Target General Infomation
Target ID
T63505
Former ID
TTDNS00592
Target Name
Proto-oncogene c-Abl
Gene Name
ABL1
Synonyms
Abelson murine leukemia viral oncogene homolog 1; Abelson tyrosine-protein kinase 1; Tyrosine-protein kinase ABL1; p150; Proto-oncogene tyrosine-protein kinase ABL1; Abl; C-ABL; ABL1
Target Type
Successful
Disease Advanced breast cancer [ICD9: 174, 175; ICD10: C50]
Acute lymphoblastic leukemia [ICD9: 204.0, 556; ICD10: C91.0]
Acute myeloid leukemia [ICD9: 205; ICD10: C92.0]
Bone disease; Chronic lymphocytic leukaemia; Metastatic hormone refractory prostate cancer [ICD9:185; ICD10: M00-M99, C91, C61]
Chronic myelogenous leukaemia [ICD9: 205.1; ICD10: C92.1]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Dietary shortage [ICD9: 260-269; ICD10: E40-E46]
Glioma; Lung cancer; Prostate cancer; Solid tumours [ICD9: 140-199, 191, 210-229; ICD10: C00-C75, C71, C7A, C7B, D10-D36, D3A]
Intestinal cancer; Myeloid leukemia [ICD9: 152, 153, 205; ICD10: C17, C18, C92]
Ischemia [ICD9: 459.89; ICD10: I99.8]
Leukemia [ICD9: 208.9; ICD10: C90-C95]
Multiple myeloma [ICD9: 203; ICD10: C90]
Osteosarcoma; Hematological malignancies; Solid tumours [ICD9: 140-199, 140-239, 170, 200-209, 210-229; ICD10: C40-C41, C81-C86, D10-D36, D3A]
Function
Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage- induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin- associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1.
BioChemical Class
Kinase
Target Validation
T78144
UniProt ID
EC Number
EC 2.7.10.2
Sequence
MLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWNSKENLLAGPSE
NDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKNGQGWVPSNYITPVN
SLEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTAS
DGKLYVSSESRFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERT
DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQ
LLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFI
HRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKS
DVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNP
SDRPSFAEIHQAFETMFQESSISDEVEKELGKQGVRGAVSTLLQAPELPTKTRTSRRAAE
HRDTTDVPEMPHSKGQGESDPLDHEPAVSPLLPRKERGPPEGGLNEDERLLPKDKKTNLF
SALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGEEEGRDISNGALAFTPLDTADPAKSP
KPSNGAGVPNGALRESGGSGFRSPHLWKKSSTLTSSRLATGEEEGGGSSSKRFLRSCSAS
CVPHGAKDTEWRSVTLPRDLQSTGRQFDSSTFGGHKSEKPALPRKRAGENRSDQVTRGTV
TPPPRLVKKNEEAADEVFKDIMESSPGSSPPNLTPKPLRRQVTVAPASGLPHKEEAGKGS
ALGTPAAAEPVTPTSKAGSGAPGGTSKGPAEESRVRRHKHSSESPGRDKGKLSRLKPAPP
PPPAASAGKAGGKPSQSPSQEAAGEAVLGAKTKATSLVDAVNSDAAKPSQPGEGLKKPVL
PATPKPQSAKPSGTPISPAPVPSTLPSASSALAGDQPSSTAFIPLISTRVSLRKTRQPPE
RIASGAITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNK
FAFREAINKLENNLRELQICPATAGSGPAATQDFSKLLSSVKEISDIVQR
Structure
1AB2; 1ABL; 1AWO; 1BBZ; 1JU5; 1OPL; 1ZZP; 2ABL; 2E2B; 2F4J; 2FO0; 2G1T; 2G2F; 2G2H; 2G2I; 2GQG; 2HIW; 2HYY; 2HZ0; 2HZ4; 2HZI; 2O88; 2V7A; 3CS9; 3EG0; 3EG1; 3EG2; 3EG3; 3EGU; 3K2M; 3PYY; 3QRI; 3QRJ; 3QRK; 3T04; 3UE4; 3UYO; 4J9B; 4J9C; 4J9D; 4J9E; 4J9F; 4J9G; 4J9H; 4J9I; 4JJB; 4JJC; 4JJD
Drugs and Mode of Action
Drug(s) Adenosine triphosphate Drug Info Approved Dietary shortage [536838]
Bosutinib Drug Info Approved Advanced breast cancer [525021], [541049]
Dasatinib Drug Info Approved Chronic myelogenous leukaemia [528715], [536577], [541021], [551871]
Imatinib Drug Info Approved Chronic myelogenous leukaemia [536294], [541030]
Nilotinib Drug Info Approved Chronic myelogenous leukaemia [529282], [541038]
Ponatinib Drug Info Approved Acute lymphoblastic leukemia [532210], [541188]
SKI-758 Drug Info Approved Ischemia [532210], [551871]
Imatinib Drug Info Phase 3 Intestinal cancer; Myeloid leukemia [536294], [541030]
AN-019 Drug Info Phase 2 Chronic myelogenous leukaemia [549038]
AZD0530 Drug Info Phase 2 Osteosarcoma; Hematological malignancies; Solid tumours [536957], [542701]
Bafetinib Drug Info Phase 2 Bone disease; Chronic lymphocytic leukaemia; Metastatic hormone refractory prostate cancer [523198], [542828]
Dasatinib Drug Info Phase 2 Multiple myeloma [536957], [541021]
Flumatinib Drug Info Phase 2 Chronic myelogenous leukaemia [525279]
Imatinib Drug Info Phase 2 Glioma; Lung cancer; Prostate cancer; Solid tumours [536294], [541030]
NPB-001-056 Drug Info Phase 1/2 Chronic myelogenous leukaemia [549228]
ABL 001 Drug Info Phase 1 Leukemia [549541]
Adaphostin Drug Info Phase 1 Chronic myelogenous leukaemia [528231]
DCC-2036 Drug Info Phase 1 Acute lymphoblastic leukemia [522553]
KW-2449 Drug Info Phase 1 Acute myeloid leukemia [530222], [541033]
MC-2001 Drug Info Preclinical Leukemia [548002]
Inhibitor (E)-4-(3,5-dimethoxystyryl)phenol Drug Info [528198]
3'',5''-dimethoxy-[1,1':2',1'']-terphenyl-4-ol Drug Info [528198]
3'',5''-dimethoxy-[1,1':3',1'']-terphenyl-4-ol Drug Info [528198]
4,3'',5''-trimethoxy-[1,1':2',1'']-terphenyl Drug Info [528198]
4,3'',5''-trimethoxy-[1,1':3',1'']-terphenyl Drug Info [528198]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol Drug Info [528490]
ABL 001 Drug Info [551798]
Adaphostin Drug Info [526238]
Adenosine triphosphate Drug Info [535436], [536557]
AG-1879 Drug Info [529296]
AN-019 Drug Info [532119]
AP-24163 Drug Info [530949]
AP-24226 Drug Info [530949]
BAS-00387275 Drug Info [528211]
BAS-00387328 Drug Info [528211]
BAS-00387347 Drug Info [528211]
BAS-00672722 Drug Info [528211]
BAS-01373578 Drug Info [528211]
BAS-0338872 Drug Info [529217]
BAS-0338876 Drug Info [529217]
BAS-09534324 Drug Info [528211]
Bis-(5-hydroxy-1H-indol-2-yl)-methanone Drug Info [528209]
Bosutinib Drug Info [536474]
Dasatinib Drug Info [536331], [536474], [536797]
Flumatinib Drug Info [532541]
Imatinib Drug Info [536474]
JNJ-10198409 Drug Info [527932]
MC-2001 Drug Info [526836]
MYRISTIC ACID Drug Info [551374]
NPB-001-056 Drug Info [531495]
ON-044580 Drug Info [531107]
PD-0166326 Drug Info [530497]
PD-0173955 Drug Info [528432]
PD-0173956 Drug Info [530497]
SKI-758 Drug Info [528584]
TG-100435 Drug Info [528527]
TRISMETHOXYRESVERATROL Drug Info [528198]
[1,1':2',1'']-terphenyl-4,3'',5''-triol Drug Info [528198]
Modulator AZD0530 Drug Info
Bafetinib Drug Info [1572591]
DCC-2036 Drug Info
Nilotinib Drug Info [529282]
Ponatinib Drug Info [551871]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
DRM DRM Info
Pathways
KEGG Pathway ErbB signaling pathway
Ras signaling pathway
Cell cycle
Axon guidance
Neurotrophin signaling pathway
Pathogenic Escherichia coli infection
Shigellosis
Pathways in cancer
MicroRNAs in cancer
Chronic myeloid leukemia
Viral myocarditis
PANTHER Pathway Axon guidance mediated by Slit/Robo
Pathway Interaction Database p73 transcription factor network
ATM pathway
Regulation of Telomerase
Posttranslational regulation of adherens junction stability and dissassembly
Lissencephaly gene (LIS1) in neuronal migration and development
PDGFR-beta signaling pathway
Neurotrophic factor-mediated Trk receptor signaling
Validated transcriptional targets of TAp63 isoforms
p53 pathway
Regulation of retinoblastoma protein
Reactome Regulation of actin dynamics for phagocytic cup formation
CDO in myogenesis
RHO GTPases Activate WASPs and WAVEs
HDR through Single Strand Annealing (SSA)
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
Factors involved in megakaryocyte development and platelet production
WikiPathways Apoptosis-related network due to altered Notch3 in ovarian cancer
Fcgamma receptor (FCGR) dependent phagocytosis
ATM Signaling Pathway
Retinoblastoma (RB) in Cancer
Integrated Pancreatic Cancer Pathway
Pathogenic Escherichia coli infection
Regulation of Microtubule Cytoskeleton
Integrated Breast Cancer Pathway
Signaling by Robo receptor
Myogenesis
Factors involved in megakaryocyte development and platelet production
References
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Ref 523198ClinicalTrials.gov (NCT01215799) Study of Bafetinib (INNO-406) as Treatment for Patients With Hormone-Refractory Prostate Cancer. U.S. National Institutes of Health.
Ref 525021ClinicalTrials.gov (NCT02311998) Phase I/II Study of Bosutinib in Combination With Inotuzumab Ozogamicin in CD22-positive Philadelphia-Chromosome (PC) Positive Acute Lymphoblastic Leukemia (ALL) and Chronic Myeloid Leukemia (CML). U.S. National Institutes of Health.
Ref 525279ClinicalTrials.gov (NCT02511340) A Phase II Study to Evaluate the Efficacy and the Safety of Flumatinib in CML-AP or CML-BP Patients.
Ref 528231New strategies in chronic myeloid leukemia. Int J Hematol. 2006 May;83(4):289-93.
Ref 5287152006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
Ref 5292822007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
Ref 530222KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17.
Ref 532210Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
Ref 536294Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
Ref 536577Dasatinib: 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 536838Emerging drugs for chemotherapy-induced mucositis. Expert Opin Emerg Drugs. 2008 Sep;13(3):511-22.
Ref 536957Current and future treatments of bone metastases. Expert Opin Emerg Drugs. 2008 Dec;13(4):609-27.
Ref 541021(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 541030(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 541033(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: 5691).
Ref 541038(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 541049(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: 5710).
Ref 541188(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: 5890).
Ref 542701(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: 7731).
Ref 542828(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 548002Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021088)
Ref 549038Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031662)
Ref 549228Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033940)
Ref 549541Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800040192)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref
Ref 526238Effects 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 526836Vascular endothelial growth factor and its receptors in multiple myeloma. Leukemia. 2003 Oct;17(10):1961-6.
Ref 527932J Med Chem. 2005 Dec 29;48(26):8163-73.(6,7-Dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamines: platelet-derived growth factor receptor tyrosine kinase inhibitors with broad antiproliferative activity against tumor cells.
Ref 528198J Med Chem. 2006 May 18;49(10):3012-8.Identification of a terphenyl derivative that blocks the cell cycle in the G0-G1 phase and induces differentiation in leukemia cells.
Ref 528209J Med Chem. 2006 Jun 1;49(11):3101-15.Novel bis(1H-indol-2-yl)methanones as potent inhibitors of FLT3 and platelet-derived growth factor receptor tyrosine kinase.
Ref 528211J Med Chem. 2006 Jun 1;49(11):3278-86.A combination of docking/dynamics simulations and pharmacophoric modeling to discover new dual c-Src/Abl kinase inhibitors.
Ref 528432J Med Chem. 2006 Sep 21;49(19):5759-68.Structural insights into the ATP binding pocket of the anaplastic lymphoma kinase by site-directed mutagenesis, inhibitor binding analysis, and homology modeling.
Ref 528490J Med Chem. 2006 Nov 2;49(22):6500-9.4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects.
Ref 528527Bioorg Med Chem Lett. 2007 Feb 1;17(3):602-8. Epub 2006 Nov 7.Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinase inhibitor with anti-tumor activity in preclinical assays.
Ref 528584J Med Chem. 2006 Dec 28;49(26):7868-76.Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles.
Ref 529217Bioorg Med Chem Lett. 2008 Feb 1;18(3):1207-11. Epub 2007 Dec 4.Discovery and SAR of 1,3,4-thiadiazole derivatives as potent Abl tyrosine kinase inhibitors and cytodifferentiating agents.
Ref 5292822007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
Ref 529296J Med Chem. 2008 Mar 13;51(5):1252-9. Epub 2008 Feb 8.Structure-based optimization of pyrazolo[3,4-d]pyrimidines as Abl inhibitors and antiproliferative agents toward human leukemia cell lines.
Ref 530222KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17.
Ref 530497Bioorg Med Chem Lett. 2009 Dec 15;19(24):6872-6. Epub 2009 Oct 23.Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors.
Ref 530949J Med Chem. 2010 Jun 24;53(12):4701-19.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.
Ref 531107A Non-ATP-Competitive Dual Inhibitor of JAK2 and BCR-ABL Kinases: Elucidation of a Novel Therapeutic Spectrum Based on Substrate Competitive Inhibition. Genes Cancer. 2010 Apr;1(4):331-45.
Ref 531495NPB001-05 inhibits Bcr-Abl kinase leading to apoptosis of imatinib-resistant cells. Front Biosci (Elite Ed). 2011 Jun 1;3:1273-88.
Ref 532119Design, synthesis and preclinical evaluation of NRC-AN-019. Int J Oncol. 2013 Jan;42(1):168-78.
Ref 532541Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25.
Ref 535436High 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. 2002 May 1;99(9):3472-5.
Ref 536331Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42. Epub 2006 Nov 28.
Ref 536474A 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 536557Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm. 2007 Dec 15;64(24 Suppl 15):S9-15.
Ref 536797In 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. Epub 2008 Aug 1.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551798ABL001, 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 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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