Drug (ID: DG01619) and It's Reported Resistant Information
Name
BAY1125976
Synonyms
BAY1125976; 1402608-02-9; BAY-1125976; UNII-ZL7A1UM87X; ZL7A1UM87X; 2-[4-(1-aminocyclobutyl)phenyl]-3-phenylimidazo[1,2-b]pyridazine-6-carboxamide; Imidazo[1,2-b]pyridazine-6-carboxamide, 2-[4-(1-aminocyclobutyl)phenyl]-3-phenyl-; 1402608-02-9 (free base); 2-(4-(1-aminocyclobutyl)phenyl)-3-phenylimidazo[1,2-b]pyridazine-6-carboxamide; 2-(4-(1-Aminocyclobutyl)phenyl)-3-phenylimidazo(1,2-b)pyridazine-6-carboxamide; Imidazo(1,2-b)pyridazine-6-carboxamide, 2-(4-(1-aminocyclobutyl)phenyl)-3-phenyl-; CHEMBL4751394; SCHEMBL12986078; US9604989, Example 5; GTPL10908; BDBM312517; BCP20659; CGC60802; EX-A3015; BAY112576; NSC793324; s8500; ZINC205604296; BAY-112576; CS-6212; NSC-793324; SB19771; BAY 1125976; Example 5 [WO2012136776A1]; AC-33646; HY-100018; BAY1125976;BAY 1125976; A921724
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Indication
In total 2 Indication(s)
Renal cell carcinoma [ICD-11: 2C90]
Phase 1
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 1
[1]
Structure
Target Proto-oncogene c-Met (MET) MET_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
4
IsoSMILES
C1CC(C1)(C2=CC=C(C=C2)C3=C(N4C(=N3)C=CC(=N4)C(=O)N)C5=CC=CC=C5)N
InChI
InChI=1S/C23H21N5O/c24-22(29)18-11-12-19-26-20(21(28(19)27-18)16-5-2-1-3-6-16)15-7-9-17(10-8-15)23(25)13-4-14-23/h1-3,5-12H,4,13-14,25H2,(H2,24,29)
InChIKey
JBGYKRAZYDNCNV-UHFFFAOYSA-N
PubChem CID
70817911
TTD Drug ID
D0LW0T
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  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
Anal canal cancer [ICD-11: 2C00]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [1]
Molecule Alteration Missense mutation
p.E17K (c.49G>A)
Sensitive Disease Anal canal cancer [ICD-11: 2C00.0]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco-2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
NCI-60 cells N.A. Homo sapiens (Human) N.A.
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
T47D cells Pleural effusion Homo sapiens (Human) CVCL_0553
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of BAY1125976 by aberration of the drug's therapeutic target
Breast cancer [ICD-11: 2C60]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [1]
Molecule Alteration Missense mutation
p.E17K (c.49G>A)
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco-2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
NCI-60 cells N.A. Homo sapiens (Human) N.A.
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
T47D cells Pleural effusion Homo sapiens (Human) CVCL_0553
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of BAY1125976 by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase alpha (PIK3CA) [1]
Molecule Alteration Missense mutation
p.K111N (c.333G>C)
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco-2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
NCI-60 cells N.A. Homo sapiens (Human) N.A.
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
T47D cells Pleural effusion Homo sapiens (Human) CVCL_0553
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.K111N (c.333G>C) in gene PIK3CA cause the sensitivity of BAY1125976 by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase alpha (PIK3CA) [1]
Molecule Alteration Missense mutation
p.P539R (c.1616C>G)
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco-2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
NCI-60 cells N.A. Homo sapiens (Human) N.A.
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
T47D cells Pleural effusion Homo sapiens (Human) CVCL_0553
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.P539R (c.1616C>G) in gene PIK3CA cause the sensitivity of BAY1125976 by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase alpha (PIK3CA) [1]
Molecule Alteration Missense mutation
p.E545K (c.1633G>A)
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco-2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
NCI-60 cells N.A. Homo sapiens (Human) N.A.
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
T47D cells Pleural effusion Homo sapiens (Human) CVCL_0553
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of BAY1125976 by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase alpha (PIK3CA) [1]
Molecule Alteration Missense mutation
p.H1047R (c.3140A>G)
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco-2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
NCI-60 cells N.A. Homo sapiens (Human) N.A.
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
T47D cells Pleural effusion Homo sapiens (Human) CVCL_0553
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.H1047R (c.3140A>G) in gene PIK3CA cause the sensitivity of BAY1125976 by unusual activation of pro-survival pathway
Key Molecule: Phosphatase and tensin homolog (PTEN) [1]
Molecule Alteration Missense mutation
p.L108R (c.323T>G)
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco-2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
NCI-60 cells N.A. Homo sapiens (Human) N.A.
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
T47D cells Pleural effusion Homo sapiens (Human) CVCL_0553
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.L108R (c.323T>G) in gene PTEN cause the sensitivity of BAY1125976 by unusual activation of pro-survival pathway
References
Ref 1 BAY 1125976, a selective allosteric AKT1/2 inhibitor, exhibits high efficacy on AKT signaling-dependent tumor growth in mouse modelsInt J Cancer. 2017 Jan 15;140(2):449-459. doi: 10.1002/ijc.30457. Epub 2016 Oct 20.

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