Drug Information

Drug (ID: DG01570) and It's Reported Resistant Information
Name
NMS-P715
Synonyms
NMS-P715; 1202055-32-0; CHEMBL1236095; N-(2,6-Diethylphenyl)-1-Methyl-8-({4-[(1-Methylpiperidin-4-Yl)carbamoyl]-2-(Trifluoromethoxy)phenyl}amino)-4,5-Dihydro-1h-Pyrazolo[4,3-H]quinazoline-3-Carboxamide; N-(2,6-diethylphenyl)-1-methyl-8-[4-[(1-methylpiperidin-4-yl)carbamoyl]-2-(trifluoromethoxy)anilino]-4,5-dihydropyrazolo[4,3-h]quinazoline-3-carboxamide; NMSP715; GTPL9401; NMS P715; SCHEMBL1558596; NMSP715; NMSP 715; BCP28244; NMS P715;NMS-P 715; BDBM50349102; ZINC58649424; CS-3396; compound 15 [PMID: 21723120]; NCGC00390549-01; AC-30241; HY-12382; B5819; FT-0702072; A910501; Q27465504; 1H-Pyrazolo[4,3-h]quinazoline-3-carboxamide, N-(2,6-diethylphenyl)-4,5-dihydro-1-methyl-8-[[4-[[(1-methyl-4-piperidinyl)amino]carbonyl]-2-(trifluoromethoxy)phenyl]amino]-
    Click to Show/Hide
Indication
In total 1 Indication(s)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Investigative
[1]
Structure
Target PI3-kinase gamma (PIK3CG) PK3CG_HUMAN [1]
Serine/threonine-protein kinase mTOR (mTOR) MTOR_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
9
IsoSMILES
CCC1=C(C(=CC=C1)CC)NC(=O)C2=NN(C3=C2CCC4=CN=C(N=C43)NC5=C(C=C(C=C5)C(=O)NC6CCN(CC6)C)OC(F)(F)F)C
InChI
InChI=1S/C35H39F3N8O3/c1-5-20-8-7-9-21(6-2)28(20)42-33(48)30-25-12-10-23-19-39-34(43-29(23)31(25)46(4)44-30)41-26-13-11-22(18-27(26)49-35(36,37)38)32(47)40-24-14-16-45(3)17-15-24/h7-9,11,13,18-19,24H,5-6,10,12,14-17H2,1-4H3,(H,40,47)(H,42,48)(H,39,41,43)
InChIKey
JFOAJUGFHDCBJJ-UHFFFAOYSA-N
PubChem CID
44556162
TTD Drug ID
D0D8JB
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
Click to Show/Hide the Resistance Disease of This Class
Colon cancer [ICD-11: 2B90]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Catenin beta-1 (CTNNB1) [1]
Molecule Alteration IF-deletion
p.S45delS (c.133_135delTCT)
 Molecule Info 
Sensitive Disease Colon cancer [ICD-11: 2B90.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
SW48 cells Colon Homo sapiens (Human) CVCL_1724
TOV-21G cells Ovary Homo sapiens (Human) CVCL_3613
HuTu80 cells Small intestine Homo sapiens (Human) CVCL_1301
TOV-112D cells Ovary Homo sapiens (Human) CVCL_3612
LS 174T cells Colon Homo sapiens (Human) CVCL_1384
A427 cells Lung Homo sapiens (Human) CVCL_1055
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Gene set analysis
Experiment for
Drug Resistance		 Cell proliferation assay
Mechanism Description The if-deletion p.S45delS (c.133_135delTCT) in gene CTNNB1 cause the sensitivity of NMS-P715 by unusual activation of pro-survival pathway.
Colorectal cancer [ICD-11: 2B91]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Catenin beta-1 (CTNNB1) [1]
Molecule Alteration Missense mutation
p.S45F (c.134C>T)
 Molecule Info 
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
SW48 cells Colon Homo sapiens (Human) CVCL_1724
TOV-21G cells Ovary Homo sapiens (Human) CVCL_3613
HuTu80 cells Small intestine Homo sapiens (Human) CVCL_1301
TOV-112D cells Ovary Homo sapiens (Human) CVCL_3612
LS 174T cells Colon Homo sapiens (Human) CVCL_1384
A427 cells Lung Homo sapiens (Human) CVCL_1055
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Gene set analysis
Experiment for
Drug Resistance		 Cell proliferation assay
Mechanism Description The missense mutation p.S45F (c.134C>T) in gene CTNNB1 cause the sensitivity of NMS-P715 by unusual activation of pro-survival pathway
Key Molecule: Catenin beta-1 (CTNNB1) [1]
Molecule Alteration Missense mutation
p.S33Y (c.98C>A)
 Molecule Info 
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
SW48 cells Colon Homo sapiens (Human) CVCL_1724
TOV-21G cells Ovary Homo sapiens (Human) CVCL_3613
HuTu80 cells Small intestine Homo sapiens (Human) CVCL_1301
TOV-112D cells Ovary Homo sapiens (Human) CVCL_3612
LS 174T cells Colon Homo sapiens (Human) CVCL_1384
A427 cells Lung Homo sapiens (Human) CVCL_1055
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Gene set analysis
Experiment for
Drug Resistance		 Cell proliferation assay
Mechanism Description The missense mutation p.S33Y (c.98C>A) in gene CTNNB1 cause the sensitivity of NMS-P715 by unusual activation of pro-survival pathway
Lung cancer [ICD-11: 2C25]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Catenin beta-1 (CTNNB1) [1]
Molecule Alteration Missense mutation
p.T41A (c.121A>G)
 Molecule Info 
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
SW48 cells Colon Homo sapiens (Human) CVCL_1724
TOV-21G cells Ovary Homo sapiens (Human) CVCL_3613
HuTu80 cells Small intestine Homo sapiens (Human) CVCL_1301
TOV-112D cells Ovary Homo sapiens (Human) CVCL_3612
LS 174T cells Colon Homo sapiens (Human) CVCL_1384
A427 cells Lung Homo sapiens (Human) CVCL_1055
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Gene set analysis
Experiment for
Drug Resistance		 Cell proliferation assay
Mechanism Description The missense mutation p.T41A (c.121A>G) in gene CTNNB1 cause the sensitivity of NMS-P715 by unusual activation of pro-survival pathway
References
Ref 1 TTK Inhibitors as a Targeted Therapy for CTNNB1 (Beta-catenin) Mutant CancersMol Cancer Ther. 2017 Nov;16(11):2609-2617. doi: 10.1158/1535-7163.MCT-17-0342. Epub 2017 Jul 27.

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Zhang.