DGIdb - PONATINIB Drug Record

PONATINIB chembl:CHEMBL1171837 ApprovedAntineoplasticImmunotherapy

Alternate Names:

AP-24534
ICLUSIG
PONATINIB
ICLUSIG®
PONATINIBUM
AP24534
AP 24534
chembl:CHEMBL1171837
drugbank:08901
rxcui:1364347
pubchem.compound:24826799
chemidplus:943319-70-8

Drug Info:

FDA Approval	Chronic myelogenous leukemia, Acute lymphoblastic leukemia (Philadelphia chromosome positive)
Drug Class	Kinase Inhibitors
Drug Categories	cytochrome p-450 cyp2c8 substrates
Drug Class	small molecule
Drug Indications	antineoplastic agent
FDA Approval	not approved
Drug Groups	investigational
Drug Categories	cytochrome p-450 cyp2c8 inhibitors (strength unknown)
Drug Categories	cytochrome p-450 cyp3a substrates
Drug Categories	cytochrome p-450 cyp3a4 substrates with a narrow therapeutic index
Drug Categories	cytochrome p-450 cyp3a5 substrates
Drug Categories	cytochrome p-450 enzyme inhibitors
Drug Categories	cytochrome p-450 substrates
Drug Categories	hepatotoxic agents
Drug Categories	immunosuppressive agents
Drug Categories	kinase inhibitor
Drug Categories	narrow therapeutic index drugs
Drug Categories	p-glycoprotein inhibitors
Drug Categories	p-glycoprotein substrates
Drug Categories	tyrosine kinase inhibitors

(12 More Sources)

Publications:

Iqbal et al., 2013, Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era., PLoS ONE
O'Hare et al., 2009, AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance., Cancer Cell
Manrique Arechavaleta et al., 2011, Rapid and sensitive allele-specific (AS)-RT-PCR assay for detection of T315I mutation in chronic myeloid leukemia patients treated with tyrosine-kinase inhibitors., Clin. Exp. Med.
Al-Ali et al., 2004, High incidence of BCR-ABL kinase domain mutations and absence of mutations of the PDGFR and KIT activation loops in CML patients with secondary resistance to imatinib., Hematol. J.
An et al., 2010, BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review., Leuk. Res.
Hofmann et al., 2002, Ph(+) acute lymphoblastic leukemia resistant to the tyrosine kinase inhibitor STI571 has a unique BCR-ABL gene mutation., Blood
O'Hare et al., 2004, Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML., Blood
Gorre et al., 2001, Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification., Science
Minami et al., 2010, Expanded distribution of the T315I mutation among hematopoietic stem cells and progenitors in a chronic myeloid leukemia patient during imatinib treatment., Int. J. Hematol.
Giles et al., 2013, MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia., Leukemia
Yin et al., 2012, Rapid quantitative detection of the T315I mutation in patients with chronic myelogenous leukemia., Diagn. Mol. Pathol.
Chahardouli et al., 2013, Detection of BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia on imatinib., Hematology
von Bubnoff et al., 2002, BCR-ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective study., Lancet
Cortes et al., 2012, Ponatinib in refractory Philadelphia chromosome-positive leukemias., N. Engl. J. Med.
Ferri et al., 2013, Early detection and quantification of mutations in the tyrosine kinase domain of chimerical BCR-ABL1 gene combining high-resolution melting analysis and mutant-allele specific quantitative polymerase chain reaction., Leuk. Lymphoma
Qin et al., 2011, Characteristics of BCR-ABL kinase domain point mutations in Chinese imatinib-resistant chronic myeloid leukemia patients., Ann. Hematol.
Paquette et al., 2011, Frequent EVI1 translocations in myeloid blast crisis CML that evolves through tyrosine kinase inhibitors., Cancer Genet
Branford et al., 2003, Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis., Blood
Doi et al., 2009, High-resolution melting analysis for a reliable and two-step scanning of mutations in the tyrosine kinase domain of the chimerical bcr-abl gene., Int. J. Hematol.
Roche-Lestienne et al., 2002, Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment., Blood
Sharma et al., 2010, Mutations in ABL kinase domain are associated with inferior progression-free survival., Leuk. Lymphoma
Soverini et al., 2006, Presence or the emergence of a F317L BCR-ABL mutation may be associated with resistance to dasatinib in Philadelphia chromosome-positive leukemia., J. Clin. Oncol.
Cang et al., 2008, P-loop mutations and novel therapeutic approaches for imatinib failures in chronic myeloid leukemia., J Hematol Oncol
Tanneeru et al., 2013, Ponatinib is a pan-BCR-ABL kinase inhibitor: MD simulations and SIE study., PLoS ONE
Sorel et al., 2004, Evidence of ABL-kinase domain mutations in highly purified primitive stem cell populations of patients with chronic myelogenous leukemia., Biochem. Biophys. Res. Commun.
Chahardouli et al., 2013, Evaluation of T315I mutation frequency in chronic myeloid leukemia patients after imatinib resistance., Hematology
Strhakova et al., 2011, Use of direct sequencing for detection of mutations in the BCR-ABL kinase domain in Slovak patients with chronic myeloid leukemia., Neoplasma
Huang et al., 2010, Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant., J. Med. Chem.
Oyekunle et al., 2011, F317L BCR-ABL1 kinase domain mutation associated with a sustained major molecular response in a CML patient on dasatinib., Leuk. Res.
Elias et al., 2012, Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients., Hematol Rep
Branford et al., 2002, High frequency of point mutations clustered within the adenosine triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance., Blood
Miller et al., 2014, Resistant mutations in CML and Ph(+)ALL - role of ponatinib., Biologics
Elias et al., 2014, BCR-ABL kinase domain mutations, including 2 novel mutations in imatinib resistant Malaysian chronic myeloid leukemia patients-Frequency and clinical outcome., Leuk. Res.
Jones et al., 2008, Kinase domain point mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia emerge after therapy with BCR-ABL kinase inhibitors., Cancer
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
von Bubnoff et al., 2003, Inhibition of wild-type and mutant Bcr-Abl by pyrido-pyrimidine-type small molecule kinase inhibitors., Cancer Res.
Eskazan et al., 2011, Chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation are resistant to dasatinib: is that true for all the patients?, Leuk. Res.
Soverini et al., 2011, BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet., Blood
Eide et al., 2011, The ABL switch control inhibitor DCC-2036 is active against the chronic myeloid leukemia mutant BCR-ABLT315I and exhibits a narrow resistance profile., Cancer Res.
Hughes et al., 2009, Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase., J. Clin. Oncol.
Yamamoto et al., 2004, The two major imatinib resistance mutations E255K and T315I enhance the activity of BCR/ABL fusion kinase., Biochem. Biophys. Res. Commun.
Soverini et al., 2011, Low-level Bcr-Abl mutations are very rare in chronic myeloid leukemia patients who are in major molecular response on first-line nilotinib., Leuk. Res.
Hochhaus et al., 2002, Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy., Leukemia
Li SQ et al., 2013, Targeting wild-type and mutationally activated FGFR4 in rhabdomyosarcoma with the inhibitor ponatinib (AP24534)., PLoS One
Gozgit et al., 2013, Combined targeting of FGFR2 and mTOR by ponatinib and ridaforolimus results in synergistic antitumor activity in FGFR2 mutant endometrial cancer models., Cancer Chemother. Pharmacol.
Gozgit et al., 2012, Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models., Mol. Cancer Ther.
Capelletti et al., 2014, Identification of recurrent FGFR3-TACC3 fusion oncogenes from lung adenocarcinoma., Clin. Cancer Res.
Goyal et al., 2017, Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive Cholangiocarcinoma., Cancer Discov
Ren et al., 2013, Novel FGFR inhibitor ponatinib suppresses the growth of non-small cell lung cancer cells overexpressing FGFR1., Oncol. Rep.
2015, Let's be pragmatic about clinical data., Sci Data
Agelopoulos et al., 2015, Deep Sequencing in Conjunction with Expression and Functional Analyses Reveals Activation of FGFR1 in Ewing Sarcoma., Clin. Cancer Res.
Wynes et al., 2014, FGFR1 mRNA and protein expression, not gene copy number, predict FGFR TKI sensitivity across all lung cancer histologies., Clin. Cancer Res.
Kancha et al., 2007, Sensitivity toward sorafenib and sunitinib varies between different activating and drug-resistant FLT3-ITD mutations., Exp. Hematol.
Mardis et al., 2009, Recurring mutations found by sequencing an acute myeloid leukemia genome., N. Engl. J. Med.
Shah et al., 2013, Ponatinib in patients with refractory acute myeloid leukaemia: findings from a phase 1 study., Br. J. Haematol.
Knapper et al., 2006, A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy., Blood
Piloto et al., 2007, Prolonged exposure to FLT3 inhibitors leads to resistance via activation of parallel signaling pathways., Blood
Smith et al., 2013, Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD., Blood
Zimmerman et al., 2013, Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia., Blood
Clark et al., 2004, Variable sensitivity of FLT3 activation loop mutations to the small molecule tyrosine kinase inhibitor MLN518., Blood
Allen et al., 2013, The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia., Leukemia
Martelli et al., 2013, Mutational landscape of AML with normal cytogenetics: biological and clinical implications., Blood Rev.
Yamamoto et al., 2001, Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies., Blood
Smith et al., 2012, Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia., Nature
Gozgit et al., 2011, Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies., Mol. Cancer Ther.
Wang et al., 2012, MicroRNAs in liver disease., Gastroenterology
Zhang et al., 2014, Reversal of acquired drug resistance in FLT3-mutated acute myeloid leukemia cells via distinct drug combination strategies., Clin. Cancer Res.
Smith et al., 2013, The role of kinase inhibitors in the treatment of patients with acute myeloid leukemia., Am Soc Clin Oncol Educ Book
Man et al., 2012, Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation., Blood
Fischer et al., 2010, Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3., J. Clin. Oncol.
Bagrintseva et al., 2004, Mutations in the tyrosine kinase domain of FLT3 define a new molecular mechanism of acquired drug resistance to PTK inhibitors in FLT3-ITD-transformed hematopoietic cells., Blood
Mathews et al., 2007, Impact of FLT3 mutations and secondary cytogenetic changes on the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with a single agent arsenic trioxide regimen., Haematologica
Eisenhoffer et al., 2012, Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia., Nature
Jourdan et al., 2013, Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia., Blood
Brown et al., 2005, FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression., Blood
Pan et al., 2015, Development and Characterization of Bladder Cancer Patient-Derived Xenografts for Molecularly Guided Targeted Therapy., PLoS ONE
Huang et al., 2016, Preclinical Modeling of KIF5B-RET Fusion Lung Adenocarcinoma., Mol. Cancer Ther.
Mologni et al., 2013, Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase., Mol. Cell. Endocrinol.
Dabir et al., 2014, RET mutation and expression in small-cell lung cancer., J Thorac Oncol
De Falco et al., 2013, Ponatinib (AP24534) is a novel potent inhibitor of oncogenic RET mutants associated with thyroid cancer., J. Clin. Endocrinol. Metab.
Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature
Ishibashi T et al., 2016, Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells., Exp Hematol
Hammerman et al., 2011, Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer., Cancer Discov
Sadovnik et al., 2014, Identification of Ponatinib as a potent inhibitor of growth, migration, and activation of neoplastic eosinophils carrying FIP1L1-PDGFRA., Exp. Hematol.
Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
Kim et al., 2016, Antitumor effects and molecular mechanisms of ponatinib on endometrial cancer cells harboring activating FGFR2 mutations., Cancer Biol. Ther.
Dutt et al., 2008, Drug-sensitive FGFR2 mutations in endometrial carcinoma., Proc. Natl. Acad. Sci. U.S.A.
Byron et al., 2013, The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib, and ponatinib ATP-competitive inhibitors., Neoplasia
Guagnano et al., 2012, FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor., Cancer Discov
Borad et al., 2014, Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma., PLoS Genet.
Tanizaki et al., 2015, Identification of Oncogenic and Drug-Sensitizing Mutations in the Extracellular Domain of FGFR2., Cancer Res.
Jin et al., 2014, Ponatinib induces apoptosis in imatinib-resistant human mast cells by dephosphorylating mutant D816V KIT and silencing β-catenin signaling., Mol. Cancer Ther.
1976, [Pathomechanisms and progress in the therapy of hypertension. 4. Hannover Nephrological Symposium]., Med Monatsschr
Lierman et al., 2012, Ponatinib is active against imatinib-resistant mutants of FIP1L1-PDGFRA and KIT, and against FGFR1-derived fusion kinases., Leukemia
Garner et al., 2014, Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients., Clin. Cancer Res.
Aghajanian, 1976, LSD and 2-bromo-LSD: comparison on effects on serotonergic neurones and on neurones in two serotonergic projection areas, the ventral lateral geniculate and amygdala., Neuropharmacology
Gleixner et al., 2013, Synergistic growth-inhibitory effects of ponatinib and midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V., Haematologica
Silen et al., 1975, Acid-base balance in amphibian gastric mucosa., Am. J. Physiol.
Gushwa et al., 2012, Selective targeting of distinct active site nucleophiles by irreversible SRC-family kinase inhibitors., J. Am. Chem. Soc.
Ghosh C et al., 2020, A Combinatorial Strategy for Targeting <i>BRAF</i> <sup>V600E</sup>-Mutant Cancers with BRAF<sup>V600E</sup> Inhibitor (PLX4720) and Tyrosine Kinase Inhibitor (Ponatinib)., Clin Cancer Res

PONATINIB RIPK3

Interaction Score: 1.89

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Inhibition of recombinant RIPK3 in an in vitro ADP-Glo assay (Promega).

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology
PONATINIB ABL1

Interaction Score: 1.36

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor

Alteration ABL1:T315I

Alteration ABL1__BCR

PMIDs:
20512393 14745431 20537386 11861307 15256422 11423618 20963643 22772060 22306673 23676790 11853795 23190221 22870928 20697894 21872826 12623848 19466505 12130516 20367437 17114651 18828913 24236021 15381060 23540562 21895409 20513156 21489624 23355941 11964322 25349473 24456693 18615627 25157968 23409026 14559829 21605905 21562040 21505103 19652056 15194504 21762985 12399961

Sources:
DTC OncoKB FDA PharmGKB DoCM TdgClinicalTrial CIViC TTD DrugBank MyCancerGenome GuideToPharmacology CGI
PONATINIB ABI1

Interaction Score: 0.95

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB
PONATINIB BCR

Interaction Score: 0.79

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Fusion protein BCR:ABL1

Notes Pan-BCR-ABL

PMIDs:
23409026

Sources:
FDA PharmGKB DrugBank TALC
PONATINIB FLT3

Interaction Score: 0.64

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor

Alteration FLT3:D835.,Y842.

Indication/Tumor Type acute myeloid leukemia

PMIDs:
17889720 19657110 23691988 16857985 17047150 23430109 24046014 15256420 23783394 23261068 11290608 22504184 21482694 20513156 22504185 24619500 23714533 22368270 20733134 25157968 14604974 17606455 22504183 23321257 15374878

Sources:
DTC DoCM JAX-CKB CIViC TTD DrugBank MyCancerGenome CGI
PONATINIB FGFR2

Interaction Score: 0.55

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration FGFR2:M536I,M538I,I548V,N550.,E566G,L618M,K660E

Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor

Clinical Status preclinical

PMIDs:
22238366 26619011 26574622 18552176 23908597 23002168 24550739 26048680 23468082

Sources:
DoCM JAX-CKB CIViC DrugBank TALC MyCancerGenome CGI
PONATINIB RIPK1

Interaction Score: 0.47

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Inhibition of recombinant RIPK1 in an in vitro ADP-Glo assay (Promega).

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology
PONATINIB RIPK2

Interaction Score: 0.47

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Inhibition of recombinant RIPK2 in an in vitro ADP-Glo assay (Promega).

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology
PONATINIB ABL2

Interaction Score: 0.42

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
20513156

Sources:
DTC
PONATINIB KIT

Interaction Score: 0.37

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor

Alteration KIT:788-828,829-860,550-592

Alteration KIT:A829P,V654A,T670I

PMIDs:
24552773 10517 21482694 20513156 22301675 25239608 10535 23539538 2015

Sources:
DTC JAX-CKB CIViC TTD DrugBank CGI
PONATINIB RET

Interaction Score: 0.29

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

PMIDs:
27496134 23811235 25122427 23526464

Sources:
MyCancerGenomeClinicalTrial JAX-CKB CIViC TTD DrugBank TALC GuideToPharmacology
PONATINIB FGFR3

Interaction Score: 0.27

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Response Type resistant

Approval Status Preclinical - Cell line xenograft

Response Type predicted – sensitive

PMIDs:
22238366 25294908 28034880 23468082

Sources:
JAX-CKB CIViC DrugBank TALC MyCancerGenome
PONATINIB FGFR4

Interaction Score: 0.24

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
24124571 23468082

Sources:
CIViC DrugBank
PONATINIB PDGFRA

Interaction Score: 0.22

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type lung small cell carcinoma

Response Type sensitive

Approval Status Preclinical

PMIDs:
22328973 20513156 19878872 24407160

Sources:
DTC JAX-CKB CIViC DrugBank
PONATINIB FGFR1

Interaction Score: 0.22

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Indication/Tumor Type extraosseous Ewing's sarcoma

Response Type sensitive

PMIDs:
22238366 23563700 26175911 26179511 24771645 23468082

Sources:
JAX-CKB CIViC DrugBank TALC MyCancerGenome
PONATINIB CDK19

Interaction Score: 0.17

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction CDK19/cyclin C.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology
PONATINIB SRC

Interaction Score: 0.1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Pdx

Response Type no benefit

PMIDs:
26270481 19878872

Sources:
JAX-CKB TdgClinicalTrial DrugBank
PONATINIB PDGFRB

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
26703895 20513156

Sources:
DTC CIViC
PONATINIB CDK8

Interaction Score: 0.09

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction CDK8/cyclin C.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology
PONATINIB TEK

Interaction Score: 0.09

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
DrugBank
PONATINIB LYN

Interaction Score: 0.08

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
19878872

Sources:
DrugBank
PONATINIB LCK

Interaction Score: 0.06

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
23190395

Sources:
DrugBank
PONATINIB KRAS

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Ponatinib + Trametinib

Indication/Tumor Type pancreatic cancer

Response Type sensitive

PMIDs:
27338794

Sources:
JAX-CKB CGI
PONATINIB KDR

Interaction Score: 0.04

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
19878872

Sources:
DrugBank MyCancerGenome
PONATINIB BRAF

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
31937621

Sources:
CIViC
PONATINIB MET

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung small cell carcinoma

Response Type sensitive

Approval Status Preclinical

PMIDs:
25122427

Sources:
JAX-CKB
PONATINIB PIK3CA

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type urinary bladder cancer

Response Type no benefit

Approval Status Preclinical - Pdx

PMIDs:
26270481

Sources:
JAX-CKB
PONATINIB ERBB2

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Pdx

Response Type no benefit

PMIDs:
26270481

Sources:
JAX-CKB
PONATINIB EGFR

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Preclinical

PMIDs:
22238366

Sources:
JAX-CKB
PONATINIB YES1

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC

DrugBank: DB08901

Version: 5.1.7

Alternate Names:

PONATINIB DrugBank Drug Name

943319-70-8 CAS Number

Iclusig Drug Brand

Drug Info:

Drug Type small molecule

Drug Groups approved

Drug Groups investigational

Publications:

Smith et al., 2013, Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD., Blood

Iqbal et al., 2013, Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era., PLoS ONE

Gozgit et al., 2013, Combined targeting of FGFR2 and mTOR by ponatinib and ridaforolimus results in synergistic antitumor activity in FGFR2 mutant endometrial cancer models., Cancer Chemother. Pharmacol.

MyCancerGenome: PONATINIB
- Version: 20-Jun-2017
Alternate Names:

AP24534 Development Name

PONATINIB Generic Name

ICLUSIG Trade Name

Drug Info:

Drug Class Kinase Inhibitors

FDA Approval Chronic myelogenous leukemia, Acute lymphoblastic leukemia (Philadelphia chromosome positive)

Publications:
TdgClinicalTrial: PONATINIB
- Version: January-2014
Alternate Names:

Drug Info:

FDA Approval not approved

Drug Indications antineoplastic agent

Drug Class small molecule

Publications:

DTC: PONATINIB

Version: 02-September-2020

Alternate Names:

CHEMBL1171837 ChEMBL Drug ID

Drug Info:

Publications:

Huang et al., 2010, Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant., J. Med. Chem.

CGI: Ponatinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

1976, [Pathomechanisms and progress in the therapy of hypertension. 4. Hannover Nephrological Symposium]., Med Monatsschr

Garner et al., 2014, Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients., Clin. Cancer Res.

Aghajanian, 1976, LSD and 2-bromo-LSD: comparison on effects on serotonergic neurones and on neurones in two serotonergic projection areas, the ventral lateral geniculate and amygdala., Neuropharmacology

JAX-CKB: Ponatinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature

Dabir et al., 2014, RET mutation and expression in small-cell lung cancer., J Thorac Oncol

Mologni et al., 2013, Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase., Mol. Cell. Endocrinol.

DoCM: PONATINIB

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Gozgit et al., 2012, Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models., Mol. Cancer Ther.

Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.

Dutt et al., 2008, Drug-sensitive FGFR2 mutations in endometrial carcinoma., Proc. Natl. Acad. Sci. U.S.A.

CIViC: PONATINIB

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Cortes et al., 2012, Ponatinib in refractory Philadelphia chromosome-positive leukemias., N. Engl. J. Med.

Tanneeru et al., 2013, Ponatinib is a pan-BCR-ABL kinase inhibitor: MD simulations and SIE study., PLoS ONE

Miller et al., 2014, Resistant mutations in CML and Ph(+)ALL - role of ponatinib., Biologics

TALC: PONATINIB
- Version: 12-May-2016
Alternate Names:

PONATINIB Primary Drug Name

PONATINIB Drug Generic Name

AP24534 Drug Synonym

Drug Info:

Publications:
TTD: Ponatinib
- Version: 2020.06.01
Alternate Names:

D0H0EQ TTD Drug ID

Drug Info:

Publications:
GuideToPharmacology: 178102513
- Version: 29-September-2020
Alternate Names:

PONATINIB GuideToPharmacology Ligand Name

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL1171837
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
MyCancerGenomeClinicalTrial: PONATINIB
- Version: 30-February-2014
Alternate Names:

Drug Info:

Publications:
OncoKB: Ponatinib
- Version: 23-July-2020
Alternate Names:

Drug Info:

Publications:
PharmGKB: ponatinib
- Version: 18-August-2020
Alternate Names:

Drug Info:

Publications:
FDA: Ponatinib
- Version: 04-September-2020
Alternate Names:

Drug Info:

Publications:

Details of the Assay for Interaction	Inhibition of recombinant RIPK3 in an <i>in vitro</i> ADP-Glo assay (Promega).
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Drug family	BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor
Alteration	ABL1:T315I
Alteration	ABL1__BCR

Alteration	FGFR2:M536I,M538I,I548V,N550.,E566G,L618M,K660E
Drug family	BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor
Clinical Status	preclinical

Details of the Assay for Interaction	Inhibition of recombinant RIPK1 in an <i>in vitro</i> ADP-Glo assay (Promega).
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Details of the Assay for Interaction	Inhibition of recombinant RIPK2 in an <i>in vitro</i> ADP-Glo assay (Promega).
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Direct Interaction?	False
Endogenous Drug?	False
Specific Action of the Ligand	Inhibition

Response Type	resistant
Approval Status	Preclinical - Cell line xenograft
Response Type	predicted – sensitive

Indication/Tumor Type	lung small cell carcinoma
Response Type	sensitive
Approval Status	Preclinical

Notes
Indication/Tumor Type	extraosseous Ewing's sarcoma
Response Type	sensitive

Details of the Assay for Interaction	CDK19/cyclin C.
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Evidence Type	Actionable
Approval Status	Preclinical - Pdx
Response Type	no benefit

Details of the Assay for Interaction	CDK8/cyclin C.
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

combination therapy	Ponatinib + Trametinib
Indication/Tumor Type	pancreatic cancer
Response Type	sensitive

Indication/Tumor Type	urinary bladder cancer
Response Type	no benefit
Approval Status	Preclinical - Pdx

Indication/Tumor Type	non-small cell lung carcinoma
Response Type	resistant
Approval Status	Preclinical

PONATINIB	DrugBank Drug Name
943319-70-8	CAS Number
Iclusig	Drug Brand

Drug Type	small molecule
Drug Groups	approved
Drug Groups	investigational

AP24534	Development Name
PONATINIB	Generic Name
ICLUSIG	Trade Name

PONATINIB	Primary Drug Name
PONATINIB	Drug Generic Name
AP24534	Drug Synonym

PONATINIB Drug Record

PONATINIB chembl:CHEMBL1171837 ApprovedAntineoplasticImmunotherapy

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction Inhibition of recombinant RIPK3 in an <i>in vitro</i> ADP-Glo assay (Promega). Specific Action of the Ligand Inhibition Endogenous Drug? False

PMIDs: None found

Sources: GuideToPharmacology

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor Alteration ABL1:T315I Alteration ABL1__BCR

Sources: DTC OncoKB FDA PharmGKB DoCM TdgClinicalTrial CIViC TTD DrugBank MyCancerGenome GuideToPharmacology CGI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: PharmGKB

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Fusion protein BCR:ABL1 Notes Pan-BCR-ABL

PMIDs: 23409026

Sources: FDA PharmGKB DrugBank TALC

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor Alteration FLT3:D835.,Y842. Indication/Tumor Type acute myeloid leukemia

PMIDs: 17889720 19657110 23691988 16857985 17047150 23430109 24046014 15256420 23783394 23261068 11290608 22504184 21482694 20513156 22504185 24619500 23714533 22368270 20733134 25157968 14604974 17606455 22504183 23321257 15374878

Sources: DTC DoCM JAX-CKB CIViC TTD DrugBank MyCancerGenome CGI

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Alteration FGFR2:M536I,M538I,I548V,N550.,E566G,L618M,K660E Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor Clinical Status preclinical

PMIDs: 22238366 26619011 26574622 18552176 23908597 23002168 24550739 26048680 23468082

Sources: DoCM JAX-CKB CIViC DrugBank TALC MyCancerGenome CGI

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction Inhibition of recombinant RIPK1 in an <i>in vitro</i> ADP-Glo assay (Promega). Specific Action of the Ligand Inhibition Endogenous Drug? False

PMIDs: None found

Sources: GuideToPharmacology

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction Inhibition of recombinant RIPK2 in an <i>in vitro</i> ADP-Glo assay (Promega). Specific Action of the Ligand Inhibition Endogenous Drug? False

PMIDs: None found

Sources: GuideToPharmacology

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 20513156

Sources: DTC

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor Alteration KIT:788-828,829-860,550-592 Alteration KIT:A829P,V654A,T670I

PMIDs: 24552773 10517 21482694 20513156 22301675 25239608 10535 23539538 2015

Sources: DTC JAX-CKB CIViC TTD DrugBank CGI

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction? False Endogenous Drug? False Specific Action of the Ligand Inhibition

PMIDs: 27496134 23811235 25122427 23526464

Sources: MyCancerGenomeClinicalTrial JAX-CKB CIViC TTD DrugBank TALC GuideToPharmacology

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Response Type resistant Approval Status Preclinical - Cell line xenograft Response Type predicted – sensitive

PMIDs: 22238366 25294908 28034880 23468082

Sources: JAX-CKB CIViC DrugBank TALC MyCancerGenome

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info:

PMIDs: 24124571 23468082

Sources: CIViC DrugBank

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type lung small cell carcinoma Response Type sensitive Approval Status Preclinical

PMIDs: 22328973 20513156 19878872 24407160

Sources: DTC JAX-CKB CIViC DrugBank

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Notes Indication/Tumor Type extraosseous Ewing's sarcoma Response Type sensitive

PMIDs: 22238366 23563700 26175911 26179511 24771645 23468082

Sources: JAX-CKB CIViC DrugBank TALC MyCancerGenome

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction CDK19/cyclin C. Specific Action of the Ligand Inhibition Endogenous Drug? False

PMIDs: None found

Sources: GuideToPharmacology

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Evidence Type Actionable Approval Status Preclinical - Pdx Response Type no benefit

PMIDs: 26270481 19878872

Sources: JAX-CKB TdgClinicalTrial DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 26703895 20513156

Sources: DTC CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction CDK8/cyclin C. Specific Action of the Ligand Inhibition Endogenous Drug? False

PMIDs: None found

Sources: GuideToPharmacology

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Inhibition of recombinant RIPK3 in an <i>in vitro</i> ADP-Glo assay (Promega).

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor

Alteration ABL1:T315I

Alteration ABL1__BCR

Sources:
DTC OncoKB FDA PharmGKB DoCM TdgClinicalTrial CIViC TTD DrugBank MyCancerGenome GuideToPharmacology CGI

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Fusion protein BCR:ABL1

Notes Pan-BCR-ABL

PMIDs:
23409026

Sources:
FDA PharmGKB DrugBank TALC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor

Alteration FLT3:D835.,Y842.

Indication/Tumor Type acute myeloid leukemia

PMIDs:
17889720 19657110 23691988 16857985 17047150 23430109 24046014 15256420 23783394 23261068 11290608 22504184 21482694 20513156 22504185 24619500 23714533 22368270 20733134 25157968 14604974 17606455 22504183 23321257 15374878

Sources:
DTC DoCM JAX-CKB CIViC TTD DrugBank MyCancerGenome CGI

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration FGFR2:M536I,M538I,I548V,N550.,E566G,L618M,K660E

Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor

Clinical Status preclinical

PMIDs:
22238366 26619011 26574622 18552176 23908597 23002168 24550739 26048680 23468082

Sources:
DoCM JAX-CKB CIViC DrugBank TALC MyCancerGenome CGI

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Inhibition of recombinant RIPK1 in an <i>in vitro</i> ADP-Glo assay (Promega).

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Inhibition of recombinant RIPK2 in an <i>in vitro</i> ADP-Glo assay (Promega).

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology

Interaction Types & Directionality:

n/a

PMIDs:
20513156

Sources:
DTC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor

Alteration KIT:788-828,829-860,550-592

Alteration KIT:A829P,V654A,T670I

PMIDs:
24552773 10517 21482694 20513156 22301675 25239608 10535 23539538 2015

Sources:
DTC JAX-CKB CIViC TTD DrugBank CGI

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

PMIDs:
27496134 23811235 25122427 23526464

Sources:
MyCancerGenomeClinicalTrial JAX-CKB CIViC TTD DrugBank TALC GuideToPharmacology

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Response Type resistant

Approval Status Preclinical - Cell line xenograft

Response Type predicted – sensitive

PMIDs:
22238366 25294908 28034880 23468082

Sources:
JAX-CKB CIViC DrugBank TALC MyCancerGenome

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
24124571 23468082

Sources:
CIViC DrugBank

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type lung small cell carcinoma

Response Type sensitive

Approval Status Preclinical

PMIDs:
22328973 20513156 19878872 24407160

Sources:
DTC JAX-CKB CIViC DrugBank

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Indication/Tumor Type extraosseous Ewing's sarcoma

Response Type sensitive

PMIDs:
22238366 23563700 26175911 26179511 24771645 23468082

Sources:
JAX-CKB CIViC DrugBank TALC MyCancerGenome

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction CDK19/cyclin C.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Pdx

Response Type no benefit

PMIDs:
26270481 19878872

Sources:
JAX-CKB TdgClinicalTrial DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
26703895 20513156

Sources:
DTC CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction CDK8/cyclin C.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
None found

Sources:
DrugBank

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
19878872

Sources:
DrugBank

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
23190395

Sources:
DrugBank