Drug Information

Drug (ID: DG01620) and It's Reported Resistant Information

• Name: ARQ 751
• Synonyms: Vevorisertib; UNII-V6SX910Y31; V6SX910Y31; 1416775-46-6; Vevorisertib [INN]; CHEMBL4802156; SCHEMBL14322498; ARQ-751; EX-A5803; HY-137458; CS-0138665; Acetamide, N-(1-(3-(3-(4-(1-aminocyclobutyl)phenyl)-2-(2-amino-3-pyridinyl)-3H-imidazo(4,5-b)pyridin-5-yl)phenyl)-4-piperidinyl)-N-methyl-; N-[1-[3-[3-[4-(1-aminocyclobutyl)phenyl]-2-(2-aminopyridin-3-yl)imidazo[4,5-b]pyridin-5-yl]phenyl]piperidin-4-yl]-N-methylacetamide
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
• Target: RAC-alpha serine/threonine-protein kinase (AKT1); AKT1_HUMAN; [1]
• Formula: 6
• IsoSMILES: CC(=O)N(C)C1CCN(CC1)C2=CC=CC(=C2)C3=NC4=C(C=C3)N=C(N4C5=CC=C(C=C5)C6(CCC6)N)C7=C(N=CC=C7)N
• InChI: InChI=1S/C35H38N8O/c1-23(44)41(2)26-15-20-42(21-16-26)28-7-3-6-24(22-28)30-13-14-31-34(39-30)43(33(40-31)29-8-4-19-38-32(29)36)27-11-9-25(10-12-27)35(37)17-5-18-35/h3-4,6-14,19,22,26H,5,15-18,20-21,37H2,1-2H3,(H2,36,38)
• InChIKey: NZDSLYATTDIDPH-UHFFFAOYSA-N
• PubChem CID: 71138858

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Breast cancer [ICD-11: 2C60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

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: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: HCC70 cells; Breast; Homo sapiens (Human); CVCL_1270
• In Vitro Model: A2058 cells; Skin; Homo sapiens (Human); CVCL_1059
• In Vitro Model: Caco-2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: NCI-60 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: KU-19 cells; Blood; Bos taurus (Bovine); CVCL_VN09
• In Vitro Model: EVSA-T cells; Ascites; Homo sapiens (Human); CVCL_1207
• In Vitro Model: CAL-120 cells; Pleural effusion; Homo sapiens (Human); CVCL_1104
• In Vitro Model: BT-549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: BT-20 cells; Mammary gland; Homo sapiens (Human); CVCL_0178
• In Vitro Model: B16F10 cells; Skin; Mus musculus (Mouse); CVCL_0159
• In Vivo Model: Female NMRI (nu/nu) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.K111N (c.333G>C) in gene PIK3CA cause the sensitivity of ARQ 751 by aberration of the drug's therapeutic target

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: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: HCC70 cells; Breast; Homo sapiens (Human); CVCL_1270
• In Vitro Model: A2058 cells; Skin; Homo sapiens (Human); CVCL_1059
• In Vitro Model: Caco-2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: NCI-60 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: KU-19 cells; Blood; Bos taurus (Bovine); CVCL_VN09
• In Vitro Model: EVSA-T cells; Ascites; Homo sapiens (Human); CVCL_1207
• In Vitro Model: CAL-120 cells; Pleural effusion; Homo sapiens (Human); CVCL_1104
• In Vitro Model: BT-549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: BT-20 cells; Mammary gland; Homo sapiens (Human); CVCL_0178
• In Vitro Model: B16F10 cells; Skin; Mus musculus (Mouse); CVCL_0159
• In Vivo Model: Female NMRI (nu/nu) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of ARQ 751 by aberration of the drug's therapeutic target

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: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: HCC70 cells; Breast; Homo sapiens (Human); CVCL_1270
• In Vitro Model: A2058 cells; Skin; Homo sapiens (Human); CVCL_1059
• In Vitro Model: Caco-2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: NCI-60 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: KU-19 cells; Blood; Bos taurus (Bovine); CVCL_VN09
• In Vitro Model: EVSA-T cells; Ascites; Homo sapiens (Human); CVCL_1207
• In Vitro Model: CAL-120 cells; Pleural effusion; Homo sapiens (Human); CVCL_1104
• In Vitro Model: BT-549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: BT-20 cells; Mammary gland; Homo sapiens (Human); CVCL_0178
• In Vitro Model: B16F10 cells; Skin; Mus musculus (Mouse); CVCL_0159
• In Vivo Model: Female NMRI (nu/nu) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.H1047R (c.3140A>G) in gene PIK3CA cause the sensitivity of ARQ 751 by aberration of the drug's therapeutic target

Endometrial cancer [ICD-11: 2C76]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [1]

• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: HCC70 cells; Breast; Homo sapiens (Human); CVCL_1270
• In Vitro Model: A2058 cells; Skin; Homo sapiens (Human); CVCL_1059
• In Vitro Model: Caco-2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: NCI-60 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: KU-19 cells; Blood; Bos taurus (Bovine); CVCL_VN09
• In Vitro Model: EVSA-T cells; Ascites; Homo sapiens (Human); CVCL_1207
• In Vitro Model: CAL-120 cells; Pleural effusion; Homo sapiens (Human); CVCL_1104
• In Vitro Model: BT-549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: BT-20 cells; Mammary gland; Homo sapiens (Human); CVCL_0178
• In Vitro Model: B16F10 cells; Skin; Mus musculus (Mouse); CVCL_0159
• In Vivo Model: Female NMRI (nu/nu) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of ARQ 751 by aberration of the drug's therapeutic target

References

• Ref 1: Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092PLoS One. 2015 Oct 15;10(10):e0140479. doi: 10.1371/journal.pone.0140479. eCollection 2015.