Drug Information

Drug (ID: DG01567) and It's Reported Resistant Information

• Name: Pimasertib
• Synonyms: Pimasertib; 1236699-92-5; AS703026; AS-703026; Pimasertib (AS-703026); MSC1936369B; AS 703026; UNII-6ON9RK82AL; 1204531-26-9; 6ON9RK82AL; SAR 245509; MSC-1936369; N-[(2S)-2,3-dihydroxypropyl]-3-(2-fluoro-4-iodo-anilino)pyridine-4-carboxamide; N-[(2S)-2,3-dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]pyridine-4-carboxamide; C15H15FIN3O3; (S)-N-(2,3-dihydroxypropyl)-3-(2-fluoro-4-iodophenylamino)isonicotinamide; (S)-N-(2,3-dihydroxypropyl)-3-((2-fluoro-4-iodophenyl)amino)isonicotinamide; (S)-N-(2,3-dihydroxypropyl)-3-((2-fluoro-4-iodophenyl)amino)isonicotinamide.; 4-Pyridinecarboxamide, N-((2S)-2,3-dihydroxypropyl)-3-((2-fluoro-4-iodophenyl)amino)-; 4-Pyridinecarboxamide, N-[(2S)-2,3-dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]-; N-((2S)-2,3-dihydroxypropyl)-3-((2-fluoro-4-iodophenyl)amino)pyridine-4-carboxamide; N-[(2S)-2,3-dihydroxypropyl]-3-(2-fluoro-4-iodoanilino)pyridine-4-carboxamide; Pimasertib [USAN:INN]; Pimasertib (USAN/INN); Pimasertib; AS703026; N-[(2S)-2,3-Dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]-4-pyridinecarboxamide; MLS006010177; GTPL7872; QCR-17; SCHEMBL2720659; CHEMBL2107832; CHEBI:94793; DTXSID40152870; EX-A403; SYN1190; BCPP000386; AOB87391; BCP02094; MSC1936369A; BDBM50014412; MSC-1936369A; NSC755763; NSC800854; ZINC38226009; AKOS022186348; BCP9000325; CCG-269018; CS-0198; DB14904; NSC-755763; NSC-800854; EMD 1036239; EMD-1036239; NCGC00346530-01; AC-32862; AS-16324; HY-12042; SMR004701285; AS703026,MSC1936369B; SW219691-1; X7392; C71933; D10426; A857420; J-523298; BRD-K89014967-001-01-9; Q27088393; G-02443714; AS7030261236699-92-5; AS-703026;N-[(2S)-2,3-Dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]-4-pyridinecarboxamide;AS-703026
• Indication:
  In total 2 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
• Target: MAPK/ERK kinase kinase (MAP3K); NOUNIPROTAC; [1]
• Formula: 6
• IsoSMILES: C1=CC(=C(C=C1I)F)NC2=C(C=CN=C2)C(=O)NC[C@@H](CO)O
• InChI: InChI=1S/C15H15FIN3O3/c16-12-5-9(17)1-2-13(12)20-14-7-18-4-3-11(14)15(23)19-6-10(22)8-21/h1-5,7,10,20-22H,6,8H2,(H,19,23)/t10-/m0/s1
• InChIKey: VIUAUNHCRHHYNE-JTQLQIEISA-N
• PubChem CID: 44187362
• ChEBI ID: CHEBI:94793
• TTD Drug ID: D03SKL
• VARIDT ID: DR1835
• DrugBank ID: DB14904

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

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 2.55 Å; PDB: 4E26
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 3.20 Å; PDB: 4G9R

RMSD: 1.53; TM score: 0.95765; Amino acid change: V600E

• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCT15 cells; Colon; Homo sapiens (Human); CVCL_0292
• In Vitro Model: COLO205 cells; Colon; Homo sapiens (Human); CVCL_F402
• In Vivo Model: Female balb/c athymic (nu+/nu+) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of Pimasertib by aberration of the drug's therapeutic target

References

• Ref 1: Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cellsInt J Cancer. 2013 Nov;133(9):2089-101. doi: 10.1002/ijc.28236. Epub 2013 May 29.