Drug Information

Drug (ID: DG01648) and It's Reported Resistant Information

• Name: GSK321
• Synonyms: GSK321; (R)-1-(4-fluorobenzyl)-N-(3-((S)-1-hydroxyethyl)phenyl)-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide; 1816331-63-1; (7r)-1-(4-Fluorobenzyl)-N-{3-[(1s)-1-Hydroxyethyl]phenyl}-7-Methyl-5-(1h-Pyrrol-2-Ylcarbonyl)-4,5,6,7-Tetrahydro-1h-Pyrazolo[4,3-C]pyridine-3-Carboxamide; CHEMBL4215717; SCHEMBL20067448; GSK-321; BDBM195601; Q27455571; (7R)-1-[(4-fluorophenyl)methyl]-N-[3-[(1S)-1-hydroxyethyl]phenyl]-7-methyl-5-(1H-pyrrole-2-carbonyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide; 59D
• Formula: 6
• IsoSMILES: C[C@@H]1CN(CC2=C1N(N=C2C(=O)NC3=CC=CC(=C3)[C@H](C)O)CC4=CC=C(C=C4)F)C(=O)C5=CC=CN5
• InChI: InChI=1S/C28H28FN5O3/c1-17-14-33(28(37)24-7-4-12-30-24)16-23-25(27(36)31-22-6-3-5-20(13-22)18(2)35)32-34(26(17)23)15-19-8-10-21(29)11-9-19/h3-13,17-18,30,35H,14-16H2,1-2H3,(H,31,36)/t17-,18+/m1/s1
• InChIKey: IVFDDVKCCBDPQZ-MSOLQXFVSA-N
• PubChem CID: 91864709

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Acute myeloid leukemia [ICD-11: 2A60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [1]

• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Molecule Alteration: Missense mutation; p.R132C (c.394C>T)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 1.93 Å; PDB: 5GIR
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 2.20 Å; PDB: 6IO0

RMSD: 1.64; TM score: 0.30204; Amino acid change: R132C

• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HT-1080 cells; Acetabulum; Homo sapiens (Human); CVCL_0317
• In Vivo Model: Male CD-1 xenograft mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Diaphorase/resazurin coupled assay; Colony formation assay

References

• Ref 1: New IDH1 mutant inhibitors for treatment of acute myeloid leukemiaNat Chem Biol. 2015 Nov;11(11):878-86. doi: 10.1038/nchembio.1930. Epub 2015 Oct 5.