Drug Information

Drug (ID: DG00546) and It's Reported Resistant Information

• Name: MK1775
• Synonyms: MK-1775; 955365-80-7; Adavosertib; MK1775; MK 1775; AZD1775; AZD 1775; AZD-1775; UNII-K2T6HJX3I3; 1-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one; 2-Allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one; 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(4-(4-methylpiperazin-1-yl)phenylamino)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one; K2T6HJX3I3; MFCD17215200; 1-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)pyrazolo[3,4-d]pyrimidin-3-one; 1-[6-(2-Hydroxypropan-2-Yl)pyridin-2-Yl]-6-{[4-(4-Methylpiperazin-1-Yl)phenyl]amino}-2-(Prop-2-En-1-Yl)-1,2-Dihydro-3h-Pyrazolo[3,4-D]pyrimidin-3-One; 3H-Pyrazolo(3,4-d)pyrimidin-3-one, 1,2-dihydro-1-(6-(1-hydroxy-1-methylethyl)-2-pyridinyl)-6-((4-(4-methyl-1-piperazinyl)phenyl)amino)-2-(2-propen-1-yl)-; 3H-Pyrazolo[3,4-d]pyrimidin-3-one, 1,2-dihydro-1-[6-(1-hydroxy-1-methylethyl)-2-pyridinyl]-6-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-2-(2-propen-1-yl)-; 8X7; Adavosertib (USAN); Kinome_2656; Adavosertib (MK-1775); MLS006011025; GTPL7702; QCR-46; SCHEMBL1504444; CHEMBL1976040; CHEBI:91414; DTXSID30241868; EX-A331; C27H32N8O2; HMS3295K03; HMS3654H20; HMS3744I13; AOB87173; BCP01928; BDBM50240826; MK-1775 (WEE-1); NSC754352; NSC800793; s1525; ZINC63539231; AKOS024259153; MK-1775(AZD-1775,Adavosertib); Adavosertib pound MK-1775 pound(c); AM90274; BCP9000937; CCG-264905; CS-0105; DB11740; NSC-754352; NSC-800793; SB16663; NCGC00263183-01; NCGC00263183-09; NCGC00263183-10; 2-allyl-1-(6-(2-hydroxy-2-propanyl)-2-pyridinyl)-6-((4-(4-methyl-1-piperazinyl)phenyl)amino)-1,2-dihydro-3H-pyrazolo(3,4-d)pyrimidin-3-one; 2-Allyl-1-[6-(2-hydroxy-2-propyl)-2-pyridyl]-6-[[4-(4-methyl-1-piperazinyl)phenyl]amino]pyrazolo[3,4-d]pyrimidin-3(2H)-one; AC-28416; AS-17001; BM161385; HY-10993; SMR004702820; SY258875; FT-0699265; SW218122-2; X7493; D11361; BRD-K54256913-001-01-2; Q27074716; 1075739-30-8; 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(4-(4-methylpiperazin-1-yl)phenylamino)-1,2-dihydropyrazolo[3,4-d]pyrimidin-3-one; 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(4-(4-methylpiperazin-1-yl)phenylamino)-1H-pyrazo; 2-Allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-pyridin-2-yl]-6-[4-(4-methyl-piperazin-1-yl)-phenylamino]-1,2-dihydro-pyrazolo[3,4-d]pyrimidin-3-one; 2-Allyl-1-[6-(1-hydroxy-1-methylethyl)pyridin-2-yl]-6-[[4-(4-methylpiperazin-1-yl)phenyl]amino]-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one
• Indication:
  In total 2 Indication(s)
  Ovarian cancer [ICD-11: 2C73]; Investigative; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Investigative; [1]
• Target: Wee1-like protein kinase (WEE1); WEE1_HUMAN; [1]
• Formula: C27H32N8O2
• IsoSMILES: CC(C)(C1=NC(=CC=C1)N2C3=NC(=NC=C3C(=O)N2CC=C)NC4=CC=C(C=C4)N5CCN(CC5)C)O
• InChI: 1S/C27H32N8O2/c1-5-13-34-25(36)21-18-28-26(29-19-9-11-20(12-10-19)33-16-14-32(4)15-17-33)31-24(21)35(34)23-8-6-7-22(30-23)27(2,3)37/h5-12,18,37H,1,13-17H2,2-4H3,(H,28,29,31)
• InChIKey: BKWJAKQVGHWELA-UHFFFAOYSA-N
• PubChem CID: 24856436
• ChEBI ID: CHEBI:91414
• TTD Drug ID: D02KKA
• DrugBank ID: DB11740

Type(s) of Resistant Mechanism of This Drug

  RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Mature T-cell lymphoma [ICD-11: 2A90]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Wee1-like protein kinase (WEE1) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Acute T-cell lymphocytic leukemia [ICD-11: 2A90.5]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: CCRF-CEM cells; Pleural effusion; Homo sapiens (Human); CVCL_0207
• In Vitro Model: MOLT4 cells; Bone marrow; Homo sapiens (Human); CVCL_0013
• In Vitro Model: DND41 cells; Pleural effusion; Homo sapiens (Human); CVCL_2022
• In Vitro Model: HPB-ALL cells; Peripheral blood; Homo sapiens (Human); CVCL_1820
• In Vitro Model: CUTLL1 cells; Pleural effusion; Homo sapiens (Human); CVCL_4966
• In Vitro Model: KOPTK1 cells; N.A.; Homo sapiens (Human); CVCL_4965
• In Vivo Model: NOD-Prkdcscid IL2Rgamma null NPG mice model; Mus musculus
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: WEE1 inhibition sensitizes T-cell acute lymphoblastic leukemia cells to glutaminolysis inhibition.Elevated WEE1 expression driven by MYC poses the possibility that T-ALL cells may be particularly dependent on WEE1 for cell proliferation and survival. Indeed, a selective WEE1 inhibitor MK1775 as a single agent reduced cell viability in a dose-dependent manner in seven T-ALL cell lines, whereas the effect on normal BM cells was minimal.

References

• Ref 1: WEE1 inhibition induces glutamine addiction in T-cell acute lymphoblastic leukemia .Haematologica. 2021 Jul 1;106(7):1816-1827. doi: 10.3324/haematol.2019.231126. 10.3324/haematol.2019.231126