Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTIV39N)

• DTT Name: Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I)
• Synonyms: T315I BCR-ABL; BCR-ABL T315I mutant
• Gene Name: BCR-ABL1
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Kinase
• UniProt ID: BCR_HUMAN-ABL1_HUMAN
• TTD ID: T01271
• 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
• Function: Difficult to inhibit with ATP mimetics. The mutation eliminates a critical hydrogen bonding interaction required for high-affinity binding of imatinib, nilotinib, and dasatinib and alters the topology of the ATP-binding pocket.

Molecular Interaction Atlas (MIA) of This DTT

15 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alkynyl-heteroaromatic ring compound 1	DMEZDQ4	N. A.	N. A.	Patented	[2]
Indazole derivative 5	DMM1I8R	N. A.	N. A.	Patented	[2]
PMID25656651-Compound-19a	DMSNUVZ	N. A.	N. A.	Patented	[2]
PMID25656651-Compound-19b	DMI1Z7D	N. A.	N. A.	Patented	[2]
PMID25656651-Compound-31a	DMSVQMO	N. A.	N. A.	Patented	[2]
PMID25656651-Compound-31b	DM6TGUR	N. A.	N. A.	Patented	[2]
PMID25656651-Compound-31c	DMDJGPC	N. A.	N. A.	Patented	[2]
PMID25656651-Compound-36a	DMNXVY9	N. A.	N. A.	Patented	[2]
PMID25656651-Compound-36b	DMHYDM7	N. A.	N. A.	Patented	[2]
PMID25656651-Compound-36c	DMOGKSW	N. A.	N. A.	Patented	[2]
PMID25656651-Compound-36d	DMKMY4I	N. A.	N. A.	Patented	[2]
PMID25656651-Compound-37a	DM0P4F3	N. A.	N. A.	Patented	[2]
PMID25656651-Compound-37b	DMX98YV	N. A.	N. A.	Patented	[2]
PMID25656651-Compound-37c	DM684IK	N. A.	N. A.	Patented	[2]
Pyrrolo[2,3-b]pyridine derivative 4	DMJBTZG	N. A.	N. A.	Patented	[2]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AP-24163	DMVT6Y3	Discovery agent	N.A.	Investigative	[3]
ON-044580	DMWOHDV	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]

References

• [1] Danusertib, an aurora kinase inhibitor.Expert Opin Investig Drugs.2012 Mar;21(3):383-93.
• [2] Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
• [3] 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 (AP2453... J Med Chem. 2010 Jun 24;53(12):4701-19.
• [4] A 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.