Drug Information

Drug (ID: DG01597) and It's Reported Resistant Information

• Name: Miransertib
• Synonyms: Miransertib; 1313881-70-7; ARQ-092; AKT inhibitor 2; ARQ 092 Free Base; ARQ092; ARQ 092; UNII-T1DQI1B52Y; T1DQI1B52Y; 3-[3-[4-(1-aminocyclobutyl)phenyl]-5-phenylimidazo[4,5-b]pyridin-2-yl]pyridin-2-amine; 3-(3-(4-(1-aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine; 3-[3-[4-(1-Azanylcyclobutyl)phenyl]-5-Phenyl-Imidazo[4,5-B]pyridin-2-Yl]pyridin-2-Amine; 3-(3-(4-(1-aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo(4,5-b)pyridin-2-yl)pyridin-2-amine; Miransertib [INN]; Miransertib [USAN]; Miransertib [WHO-DD]; Miransertib (USAN/INN); Miransertib [USAN:INN]; Miransertib (ARQ-092); GTPL9429; SCHEMBL2187875; CHEMBL4297188; BCP19821; EX-A1268; NSC791328; WHO 10490; ZINC72315647; CS-5377; DB14982; NSC-791328; SB19688; compound 21a [PMID: 27305487]; HY-19719; DB-105304; S6811; J3.532.768A; D11409; A922251; Q27456535; 2-Pyridinamine, 3-(3-(4-(1-aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo(4,5-b)pyridin-2-yl)-; 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo(4,5-b)pyridin-2-yl)-2-pyridinamine; 6S1
• Indication:
  In total 2 Indication(s)
  Cholangiocarcinoma [ICD-11: 2C12]; Phase 2; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
• Target: Fibroblast growth factor receptor (FGFR); NOUNIPROTAC; [2]
• Target: Fibroblast growth factor receptor 1 (FGFR1); FGFR1_HUMAN; [2]
• Formula: 4
• IsoSMILES: C1CC(C1)(C2=CC=C(C=C2)N3C4=C(C=CC(=N4)C5=CC=CC=C5)N=C3C6=C(N=CC=C6)N)N
• InChI: InChI=1S/C27H24N6/c28-24-21(8-4-17-30-24)25-32-23-14-13-22(18-6-2-1-3-7-18)31-26(23)33(25)20-11-9-19(10-12-20)27(29)15-5-16-27/h1-4,6-14,17H,5,15-16,29H2,(H2,28,30)
• InChIKey: HNFMVVHMKGFCMB-UHFFFAOYSA-N
• PubChem CID: 53262401
• TTD Drug ID: D03LWG
• DrugBank ID: DB14982

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.E542K (c.1624G>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.E542K (c.1624G>A) in gene PIK3CA cause the sensitivity of Miransertib 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 Miransertib 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 Miransertib by aberration of the drug's therapeutic target

Ovarian cancer [ICD-11: 2C73]

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) [2]

• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of Miransertib 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 Miransertib 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.
• Ref 2: First evidence of a therapeutic effect of miransertib in a teenager with Proteus syndrome and ovarian carcinomaAm J Med Genet A. 2019 Jul;179(7):1319-1324. doi: 10.1002/ajmg.a.61160. Epub 2019 May 6.