adavosertib

a Wee1 kinase inhibitor; structure in first source

Also Known As:

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; 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)-; AZD 1775; AZD-1775; AZD1775; MK 1775; MK-1775; MK1775

Networked: 192 relevant articles (33 outcomes, 76 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Heterocyclic Compounds: 198
- 1-Ring Heterocyclic Compounds
  - Azoles: 2138
    - Pyrazoles: 61
      - adavosertib: 192
  - Pyrimidines: 510
    - Pyrimidinones: 71
      - adavosertib: 192

Experts

1.	Shumway, Stuart D: 7 articles (01/2016 - 05/2011)
2.	Lawrence, Theodore S: 6 articles (10/2019 - 10/2014)
3.	Maybaum, Jonathan: 6 articles (10/2019 - 10/2014)
4.	Morgan, Meredith A: 6 articles (10/2019 - 10/2014)
5.	Li, Jing: 6 articles (01/2018 - 11/2012)
6.	Oza, Amit M: 5 articles (01/2022 - 12/2016)
7.	Venkataraman, Sujatha: 5 articles (05/2020 - 03/2014)
8.	Vibhakar, Rajeev: 5 articles (05/2020 - 03/2014)
9.	Parsels, Leslie A: 5 articles (10/2019 - 10/2014)
10.	Reigan, Philip: 5 articles (01/2018 - 12/2013)

Related Diseases

1.	Neoplasms (Cancer) 09/01/2011 - "MK-1775 also significantly enhanced the antitumor efficacy of radiation in vivo as shown in tumor growth delay studies, again for p53-defective tumors. " 06/13/2019 - "AZD1775, an orally available Wee1 inhibitor, has entered clinical trials for cancer treatment following this strategy, with promising results. " 07/01/2023 - "The safety, tolerability, pharmacokinetics, and efficacy of adavosertib monotherapy were evaluated in patients with various solid-tumor types and molecular profiles. " 09/01/2021 - "Drug susceptibility assay using an ex vivo cancer tissue-originated spheroid system showed correlations with the in vivo efficacy of AZD-1775 alone or combined with CDDP. " 06/01/2023 - "This study investigated dosing schedules for adavosertib monotherapy, determining the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) in patients with advanced solid tumors.Patients"
2.	Squamous Cell Carcinoma of Head and Neck 01/01/2021 - "In this study, we investigated the combined effect of Rad51 inhibitor (B02) and Wee1 inhibitor (AZD1775) in vitro and in vivo in various HNSCC cell lines. " 01/01/2021 - "Clonogenic survival assays demonstrated that B02 synergized with AZD1775 in vitro in all HNSCC cell lines tested. " 06/17/2019 - "In contrast, Wee1 inhibitor Adavosertib progresses the cell cycle and thereby increases lethality to Chk1 inhibition in HNSCC cell lines. " 01/01/2019 - "IMPLICATIONS: The data encourage the use of AZD1775 in combination with genotoxic modalities against p53-deficient head and neck squamous cell carcinoma." 12/01/2021 - "The authors conducted a phase 1b trial to evaluate the safety of adavosertib in combination with definitive chemoradiotherapy for patients with newly diagnosed, intermediate-risk/high-risk, locally advanced head and neck squamous cell carcinoma (HNSCC). "
3.	Ovarian Neoplasms (Ovarian Cancer) 01/01/2022 - "Taken together, the data reveal an important dual role of the UPR signaling network in mtTP53 ovarian cancer models in response to AZD1775 and suggest that inhibition of the IRE1α-XBP1s pathway may enhance the efficacy of AZD1775 in the clinics." 01/01/2017 - "The results of the present study supported the use of MK1775 as a monotherapy agent in ovarian cancer. " 01/01/2017 - "The present study aimed at examining the in vitro and in vivo antitumor activity of MK1775, a potent pharmacological inhibitor of WEE1, as a single agent against ovarian cancer cells. " 01/01/2022 - "Effects of Wee1 inhibitor adavosertib on patient-derived high-grade serous ovarian cancer cells are multiple and independent of homologous recombination status." 01/01/2022 - "Inhibiting the IRE1α Axis of the Unfolded Protein Response Enhances the Antitumor Effect of AZD1775 in TP53 Mutant Ovarian Cancer."
4.	Pancreatic Neoplasms (Pancreatic Cancer) 05/01/2011 - "Nine individual patient-derived pancreatic cancer xenografts (6 with p53-deficient and 3 with p53 wild-type status) from the PancXenoBank collection at Johns Hopkins were treated with MK-1775, GEM, or GEM followed 24 hour later by MK-1775, for 4 weeks. " 01/01/2019 - "AZD1775 plus chemoradiotherapy for pancreatic cancer." 01/01/2016 - "In this paper we applied multiparametric flow cytometry to patient-derived pancreatic cancer xenograft tumor cells to study the cell cycle perturbations of Wee1 disruption via the small molecule inhibitor MK-1775, and genetic knockdown. " 05/01/2011 - "These results indicate that MK-1775 selectively synergizes with GEM to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts." 10/10/2019 - "In this study, we built on our preclinical studies to evaluate the safety and efficacy of AZD1775 in combination with gemcitabine and radiation in patients with newly diagnosed locally advanced pancreatic cancer. "
5.	Colorectal Neoplasms (Colorectal Cancer) 01/01/2017 - "AZD1775 induces toxicity through double-stranded DNA breaks independently of chemotherapeutic agents in p53-mutated colorectal cancer cells." 01/01/2017 - "AZD1775 significantly improved the cytotoxicity of 5-FU in a p53-mutated colorectal cancer cell line (HT29 cells), decreasing the IC50 from 9.3 μM to 3.5 μM. " 11/20/2021 - "Inhibition of WEE1 Is Effective in TP53- and RAS-Mutant Metastatic Colorectal Cancer: A Randomized Trial (FOCUS4-C) Comparing Adavosertib (AZD1775) With Active Monitoring." 01/01/2017 - "In conclusion, AZD1775 enhances 5-FU cytotoxicity through increased DS-DNA breaks, not premature mitosis, in p53-mutated colorectal cancer cells. "

Related Drugs and Biologics

1.	adavosertib
2.	Gemcitabine
3.	Phosphotransferases (Kinase)
4.	Cisplatin (Platino)
5.	Platinum
6.	olaparib
7.	DNA (Deoxyribonucleic Acid)
8.	Fluorouracil (Carac)
9.	Carboplatin (JM8)
10.	Poly(ADP-ribose) Polymerase Inhibitors

Related Therapies and Procedures

1.	Therapeutics
2.	Radiotherapy
3.	Drug Therapy (Chemotherapy)
4.	Chemoradiotherapy
5.	Precision Medicine