Target Information
| Target General Information | Top | |||||
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| Target ID |
T38284
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| Target Name |
Fusion protein Bcr-Abl (Bcr-Abl)
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| Synonyms |
BCR-ABL fusion protein; BCR-ABL
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| Gene Name |
BCR-ABL1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Mature B-cell lymphoma [ICD-11: 2A85] | |||||
| 2 | Myeloproliferative neoplasm [ICD-11: 2A20] | |||||
| Function |
Activates downstream signaling pathways such as STAT5, PI3K/Akt, and Erk1/2 to lead to increased cell transformation, survival, and proliferation.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| Sequence |
MVDPVGFAEAWKAQFPDSEPPRMELRSVGDIEQELERCKASIRRLEQEVNQERFRMIYLQ
TLLAKEKKSYDRQRWGFRRAAQAPDGASEPRASASRPQPAPADGADPPPAEEPEARPDGE GSPGKARPGTARRPGAAASGERDDRGPPASVAALRSNFERIRKGHGQPGADAEKPFYVNV EFHHERGLVKVNDKEVSDRISSLGSQAMQMERKKSQHGAGSSVGDASRPPYRGRSSESSC GVDGDYEDAELNPRFLKDNLIDANGGSRPPWPPLEYQPYQSIYVGGMMEGEGKGPLLRSQ STSEQEKRLTWPRRSYSPRSFEDCGGGYTPDCSSNENLTSSEEDFSSGQSSRVSPSPTTY RMFRDKSRSPSQNSQQSFDSSSPPTPQCHKRHRHCPVVVSEATIVGVRKTGQIWPNDGEG AFHGDADGSFGTPPGYGCAADRAEEQRRHQDGLPYIDDSPSSSPHLSSKGRGSRDALVSG ALESTKASELDLEKGLEMRKWVLSGILASEETYLSHLEALLLPMKPLKAAATTSQPVLTS QQIETIFFKVPELYEIHKEFYDGLFPRVQQWSHQQRVGDLFQKLASQLGVYRAFVDNYGV AMEMAEKCCQANAQFAEISENLRARSNKDAKDPTTKNSLETLLYKPVDRVTRSTLVLHDL LKHTPASHPDHPLLQDALRISQNFLSSINEEITPRRQSMTVKKGEHRQLLKDSFMVELVE GARKLRHVFLFTDLLLCTKLKKQSGGKTQQYDCKWYIPLTDLSFQMVDELEAVPNIPLVP DEELDALKIKISQIKNDIQREKRANKGSKATERLKKKLSEQESLLLLMSPSMAFRVHSRN GKSYTFLISSDYERAEWRENIREQQKKCFRSFSLTSVELQMLTNSCVKLQTVHSIPLTIN KEDDESPGLYGFLNVIVHSATGFKQSSNLYCTLEVDSFGYFVNKAKTRVYRDTAEPNWNE EFEIELEGSQTLRILCYEKCYNKTKIPKEDGESTDRLMGKGQVQLDPQALQDRDWQRTVI AMNGIEVKLSVKFNSREFSLKRMPSRKQTGVFGVKIAVVTKRERSKVPYIVRQCVEEIER RGMEEVGIYRVSGVATDIQALKAAFDVNNKDVSVMMSEMDVNAIAGTLKLYFRELPEPLF TDEFYPNFAEGIALSDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKEAVNKMSL HNLATVFGPTLLRPSEKESKLPANPSQPITMTDSWSLEVMSQVQVLLYFLQLEAIPAPDS KRQSILFSTEVMLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWN SKENLLAGPSENDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKNGQG WVPSNYITPVNSLEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEG RVYHYRINTASDGKLYVSSESRFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTVYGVS PNYDKWEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAV MKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISS AMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPE SLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVY ELMRACWQWNPSDRPSFAEIHQAFETMFQESSISDEVEKELGKQGVRGAVSTLLQAPELP TKTRTSRRAAEHRDTTDVPEMPHSKGQGESDPLDHEPAVSPLLPRKERGPPEGGLNEDER LLPKDKKTNLFSALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGEEEGRDISNGALAFT PLDTADPAKSPKPSNGAGVPNGALRESGGSGFRSPHLWKKSSTLTSSRLATGEEEGGGSS SKRFLRSCSASCVPHGAKDTEWRSVTLPRDLQSTGRQFDSSTFGGHKSEKPALPRKRAGE NRSDQVTRGTVTPPPRLVKKNEEAADEVFKDIMESSPGSSPPNLTPKPLRRQVTVAPASG LPHKEEAGKGSALGTPAAAEPVTPTSKAGSGAPGGTSKGPAEESRVRRHKHSSESPGRDK GKLSRLKPAPPPPPAASAGKAGGKPSQSPSQEAAGEAVLGAKTKATSLVDAVNSDAAKPS QPGEGLKKPVLPATPKPQSAKPSGTPISPAPVPSTLPSASSALAGDQPSSTAFIPLISTR VSLRKTRQPPERIASGAITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVS YVDSIQQMRNKFAFREAINKLENNLRELQICPATAGSGPAATQDFSKLLSSVKEISDIVQ R Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 4 Approved Drugs | + | ||||
| 1 | Asciminib | Drug Info | Approved | Chronic myeloid leukaemia | [2] | |
| 2 | Dasatinib | Drug Info | Approved | Chronic myelogenous leukaemia | [3], [4], [5], [6] | |
| 3 | Imatinib | Drug Info | Approved | Chronic myelogenous leukaemia | [7], [8] | |
| 4 | Nilotinib | Drug Info | Approved | Chronic myelogenous leukaemia | [9], [10] | |
| Clinical Trial Drug(s) | [+] 9 Clinical Trial Drugs | + | ||||
| 1 | ABL 001 | Drug Info | Phase 3 | Chronic myeloid leukaemia | [11] | |
| 2 | ICLUSIG | Drug Info | Phase 3 | Acute lymphoblastic leukaemia | [12] | |
| 3 | Radotinib | Drug Info | Phase 3 | leukaemia | [13], [14] | |
| 4 | AN-019 | Drug Info | Phase 2 | Chronic myelogenous leukaemia | [15] | |
| 5 | Bafetinib | Drug Info | Phase 2 | Bone disease | [16], [17] | |
| 6 | HQP1351 | Drug Info | Phase 2 | Chronic myeloid leukaemia | [18] | |
| 7 | NPB-001-056 | Drug Info | Phase 1/2 | Chronic myelogenous leukaemia | [19] | |
| 8 | Adaphostin | Drug Info | Phase 1 | Chronic myelogenous leukaemia | [20] | |
| 9 | SCO-088 | Drug Info | Phase 1 | Chronic myeloid leukaemia | [21] | |
| Patented Agent(s) | [+] 4 Patented Agents | + | ||||
| 1 | PMID25656651-Compound-11a | Drug Info | Patented | Chronic myeloid leukaemia | [22] | |
| 2 | PMID25656651-Compound-11b | Drug Info | Patented | Chronic myeloid leukaemia | [22] | |
| 3 | PMID25656651-Compound-11c | Drug Info | Patented | Chronic myeloid leukaemia | [22] | |
| 4 | PMID25656651-Compound-5 | Drug Info | Patented | Chronic myeloid leukaemia | [22] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 66 Inhibitor drugs | + | ||||
| 1 | Asciminib | Drug Info | [23] | |||
| 2 | Dasatinib | Drug Info | [1], [24], [25] | |||
| 3 | Imatinib | Drug Info | [1] | |||
| 4 | ABL 001 | Drug Info | [26], [11] | |||
| 5 | ICLUSIG | Drug Info | [27] | |||
| 6 | AN-019 | Drug Info | [29] | |||
| 7 | HQP1351 | Drug Info | [31] | |||
| 8 | NPB-001-056 | Drug Info | [32] | |||
| 9 | Adaphostin | Drug Info | [33] | |||
| 10 | SCO-088 | Drug Info | [21] | |||
| 11 | Aminopyrimidine derivative 1 | Drug Info | [22] | |||
| 12 | Aminopyrimidine derivative 2 | Drug Info | [22] | |||
| 13 | Aminopyrimidine derivative 3 | Drug Info | [22] | |||
| 14 | Aminopyrimidine derivative 4 | Drug Info | [22] | |||
| 15 | Deuterated 3-cyanoquinoline derivative 1 | Drug Info | [22] | |||
| 16 | PMID25656651-Compound-10 | Drug Info | [22] | |||
| 17 | PMID25656651-Compound-11a | Drug Info | [22] | |||
| 18 | PMID25656651-Compound-11b | Drug Info | [22] | |||
| 19 | PMID25656651-Compound-11c | Drug Info | [22] | |||
| 20 | PMID25656651-Compound-15a | Drug Info | [22] | |||
| 21 | PMID25656651-Compound-15b | Drug Info | [22] | |||
| 22 | PMID25656651-Compound-15c | Drug Info | [22] | |||
| 23 | PMID25656651-Compound-16a | Drug Info | [22] | |||
| 24 | PMID25656651-Compound-16b | Drug Info | [22] | |||
| 25 | PMID25656651-Compound-18 | Drug Info | [22] | |||
| 26 | PMID25656651-Compound-19a | Drug Info | [22] | |||
| 27 | PMID25656651-Compound-19b | Drug Info | [22] | |||
| 28 | PMID25656651-Compound-20a | Drug Info | [22] | |||
| 29 | PMID25656651-Compound-20b | Drug Info | [22] | |||
| 30 | PMID25656651-Compound-21a | Drug Info | [22] | |||
| 31 | PMID25656651-Compound-21b | Drug Info | [22] | |||
| 32 | PMID25656651-Compound-23a | Drug Info | [22] | |||
| 33 | PMID25656651-Compound-23b | Drug Info | [22] | |||
| 34 | PMID25656651-Compound-23c | Drug Info | [22] | |||
| 35 | PMID25656651-Compound-25 | Drug Info | [22] | |||
| 36 | PMID25656651-Compound-26a | Drug Info | [22] | |||
| 37 | PMID25656651-Compound-26b | Drug Info | [22] | |||
| 38 | PMID25656651-Compound-26c | Drug Info | [22] | |||
| 39 | PMID25656651-Compound-27 | Drug Info | [22] | |||
| 40 | PMID25656651-Compound-29a | Drug Info | [22] | |||
| 41 | PMID25656651-Compound-29b | Drug Info | [22] | |||
| 42 | PMID25656651-Compound-30a | Drug Info | [22] | |||
| 43 | PMID25656651-Compound-30b | Drug Info | [22] | |||
| 44 | PMID25656651-Compound-36a | Drug Info | [22] | |||
| 45 | PMID25656651-Compound-36b | Drug Info | [22] | |||
| 46 | PMID25656651-Compound-36c | Drug Info | [22] | |||
| 47 | PMID25656651-Compound-36d | Drug Info | [22] | |||
| 48 | PMID25656651-Compound-37a | Drug Info | [22] | |||
| 49 | PMID25656651-Compound-37b | Drug Info | [22] | |||
| 50 | PMID25656651-Compound-37c | Drug Info | [22] | |||
| 51 | PMID25656651-Compound-38 | Drug Info | [22] | |||
| 52 | PMID25656651-Compound-40 | Drug Info | [22] | |||
| 53 | PMID25656651-Compound-5 | Drug Info | [22] | |||
| 54 | PMID25656651-Compound-7 | Drug Info | [22] | |||
| 55 | Pyridoindole derivative 1 | Drug Info | [22] | |||
| 56 | Pyridoindole derivative 2 | Drug Info | [22] | |||
| 57 | Pyridoindole derivative 3 | Drug Info | [22] | |||
| 58 | Pyrimidinyl pyrazolamine derivative 1 | Drug Info | [22] | |||
| 59 | Pyrrolo[2,3-b]pyridine carboxamide derivative 1 | Drug Info | [22] | |||
| 60 | (E)-4-(3,5-dimethoxystyryl)phenol | Drug Info | [34] | |||
| 61 | 3'',5''-dimethoxy-[1,1':2',1'']-terphenyl-4-ol | Drug Info | [34] | |||
| 62 | 3'',5''-dimethoxy-[1,1':3',1'']-terphenyl-4-ol | Drug Info | [34] | |||
| 63 | 4,3'',5''-trimethoxy-[1,1':2',1'']-terphenyl | Drug Info | [34] | |||
| 64 | 4,3'',5''-trimethoxy-[1,1':3',1'']-terphenyl | Drug Info | [34] | |||
| 65 | HKI-9924129 | Drug Info | [35] | |||
| 66 | PD-0173955 | Drug Info | [36] | |||
| Modulator | [+] 3 Modulator drugs | + | ||||
| 1 | Nilotinib | Drug Info | [10] | |||
| 2 | Radotinib | Drug Info | [28] | |||
| 3 | Bafetinib | Drug Info | [30] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22. | |||||
| REF 2 | FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 215358. | |||||
| REF 3 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5678). | |||||
| REF 4 | 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101. | |||||
| REF 5 | Dasatinib: a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia. Clin Ther. 2007 Nov;29(11):2289-308. | |||||
| REF 6 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 7 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5687). | |||||
| REF 8 | Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19. | |||||
| REF 9 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5697). | |||||
| REF 10 | 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9. | |||||
| REF 11 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 12 | ClinicalTrials.gov (NCT03589326) A Phase 3, Randomized, Open-label, Multicenter Study Comparing Ponatinib Versus Imatinib, Administered in Combination With Reduced-Intensity Chemotherapy, in Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL). U.S.National Institutes of Health. | |||||
| REF 13 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7814). | |||||
| REF 14 | ClinicalTrials.gov (NCT01511289) Radotinib Versus Imatinib in Newly Diagnosed Philadelphia Chromosome and Chronic Myeloid Leukemia Chronic Phase Patients. U.S. National Institutes of Health. | |||||
| REF 15 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031662) | |||||
| REF 16 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7906). | |||||
| REF 17 | ClinicalTrials.gov (NCT01215799) Study of Bafetinib (INNO-406) as Treatment for Patients With Hormone-Refractory Prostate Cancer. U.S. National Institutes of Health. | |||||
| REF 18 | ClinicalTrials.gov (NCT03883100) A Pivotal Study of HQP1351 in Patients of Chronic Myeloid Leukemia in Accelerated Phase With T315I Mutation. U.S. National Institutes of Health. | |||||
| REF 19 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033940) | |||||
| REF 20 | New strategies in chronic myeloid leukemia. Int J Hematol. 2006 May;83(4):289-93. | |||||
| REF 21 | Clinical pipeline report, company report or official report of Sun Pharma Advanced Research Company. | |||||
| REF 22 | Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412. | |||||
| REF 23 | Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019 Dec 12;381(24):2315-2326. | |||||
| REF 24 | In vitro and clinical investigation of the relationship between CCR5 receptor occupancy and anti-HIV activity of Aplaviroc. J Clin Pharmacol. 2008 Oct;48(10):1179-88. | |||||
| REF 25 | Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42. | |||||
| REF 26 | ABL001, a Potent Allosteric Inhibitor of BCR-ABL, Prevents Emergence of Resistant Disease When Administered in Combination with Nilotinib in an in Vivo Murine Model of Chronic Myeloid Leukemia, NorthBuilding, 2014, 120-125. | |||||
| REF 27 | Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018 Jul 26;132(4):393-404. | |||||
| REF 28 | Danusertib, an aurora kinase inhibitor.Expert Opin Investig Drugs.2012 Mar;21(3):383-93. | |||||
| REF 29 | Design, synthesis and preclinical evaluation of NRC-AN-019. Int J Oncol. 2013 Jan;42(1):168-78. | |||||
| REF 30 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 31 | Preclinical development of HQP1351, a multikinase inhibitor targeting a broad spectrum of mutant KIT kinases, for the treatment of imatinib-resistant gastrointestinal stromal tumors. Cell Biosci. 2019 Oct 26;9:88. | |||||
| REF 32 | NPB001-05 inhibits Bcr-Abl kinase leading to apoptosis of imatinib-resistant cells. Front Biosci (Elite Ed). 2011 Jun 1;3:1273-88. | |||||
| REF 33 | Effects of the Bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on chronic myelogenous leukemia cells in vitro. Blood. 2002 Jan 15;99(2):664-71. | |||||
| REF 34 | Identification of a terphenyl derivative that blocks the cell cycle in the G0-G1 phase and induces differentiation in leukemia cells. J Med Chem. 2006 May 18;49(10):3012-8. | |||||
| REF 35 | Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571). Cancer Res. 2002 Dec 15;62(24):7149-53. | |||||
| REF 36 | Structural insights into the ATP binding pocket of the anaplastic lymphoma kinase by site-directed mutagenesis, inhibitor binding analysis, and hom... J Med Chem. 2006 Sep 21;49(19):5759-68. | |||||
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