Drug Information

Drug (ID: DG01586) and It's Reported Resistant Information

• Name: Taladegib
• Synonyms: Taladegib; 1258861-20-9; LY2940680; LY-2940680; 4-Fluoro-N-methyl-N-(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)-2-(trifluoromethyl)benzamide; UNII-QY8BWX1LJ5; LY 2940680; QY8BWX1LJ5; Taladegib (LY2940680); 4-fluoro-N-methyl-N-[1-[4-(2-methylpyrazol-3-yl)phthalazin-1-yl]piperidin-4-yl]-2-(trifluoromethyl)benzamide; 4-Fluoro-N-Methyl-N-{1-[4-(1-Methyl-1h-Pyrazol-5-Yl)phthalazin-1-Yl]piperidin-4-Yl}-2-(Trifluoromethyl)benzamide; 4-fluoro-n-methyl-n-(1-(4-(1-methyl-1h-pyrazol-5-yl)-1-phthalazinyl)-4-piperidinyl)-2-(trifluoromethyl)benzamide; Benzamide, 4-fluoro-N-methyl-N-(1-(4-(1-methyl-1H-pyrazol-5-yl)-1-phthalazinyl)-4-piperidinyl)-2-(trifluoromethyl)-; Benzamide, 4-fluoro-N-methyl-N-[1-[4-(1-methyl-1H-pyrazol-5-yl)-1-phthalazinyl]-4-piperidinyl]-2-(trifluoromethyl)-; Taladegib [USAN:INN]; 4-Fluoro-N-methyl-N-{1-[4-(1-methyl-1H-pyrazol-5-yl)-1-phthalazinyl]-4-piperidinyl}-2-(trifluoromethyl)benzamide; Taladegib (USAN/INN); MLS006011066; LY-2940680(Taladegib); SCHEMBL2128615; CHEMBL2142592; C26H24F4N6O; GTPL10333; DTXSID50154986; EX-A156; BCP02512; BDBM50545020; MFCD21609264; NSC767896; s2157; ZINC68247898; AKOS026674116; BCP9000881; CCG-269788; CS-0459; DB12550; NSC-767896; SB16504; NCGC00263170-01; NCGC00263170-06; AC-33096; AS-75020; HY-13242; QC-11811; SMR004702857; X7613; D10671; J-515412; Q27287564; 1KS; LY 2940680; ; ; 4-fluoro-N-methyl-N-[1-[4-(1-methyl-1H-pyrazol-5-yl)-1-phthalazinyl]-4-piperidinyl]-2-(trifluoromethyl)-benzamide
• Indication:
  In total 3 Indication(s)
  Chronic lymphocytic leukaemia [ICD-11: 2A82]; Phase 1/2; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1/2; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1/2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [1]
• Target: Apoptosis regulator Bcl-2 (BCL-2); BCL2_HUMAN; [1]
• Formula: 4
• IsoSMILES: CN1C(=CC=N1)C2=NN=C(C3=CC=CC=C32)N4CCC(CC4)N(C)C(=O)C5=C(C=C(C=C5)F)C(F)(F)F
• InChI: InChI=1S/C26H24F4N6O/c1-34(25(37)20-8-7-16(27)15-21(20)26(28,29)30)17-10-13-36(14-11-17)24-19-6-4-3-5-18(19)23(32-33-24)22-9-12-31-35(22)2/h3-9,12,15,17H,10-11,13-14H2,1-2H3
• InChIKey: SZBGQDXLNMELTB-UHFFFAOYSA-N
• PubChem CID: 49848070
• TTD Drug ID: D00PBX
• VARIDT ID: DR1816
• DrugBank ID: DB12550

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.I408V (c.1222A>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.I408V (c.1222A>G) in gene SMO cause the resistance of Taladegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.A459V (c.1376C>T)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.A459V (c.1376C>T) in gene SMO cause the resistance of Taladegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.C469Y (c.1406G>A)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.C469Y (c.1406G>A) in gene SMO cause the resistance of Taladegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.T241M (c.722C>T)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.T241M (c.722C>T) in gene SMO cause the resistance of Taladegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.W281C (c.843G>T)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.W281C (c.843G>T) in gene SMO cause the resistance of Taladegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.V321M (c.961G>A)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.V321M (c.961G>A) in gene SMO cause the resistance of Taladegib by aberration of the drug's therapeutic target

References

• Ref 1: Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma. Cancer Cell. 2015 Mar 9;27(3):327-41. doi: 10.1016/j.ccell.2015.02.001.