Glasdegib maleateProduct ingredient for Glasdegib
- Name
- Glasdegib maleate
- Drug Entry
- Glasdegib
Glasdegib, also known as PF-04449913, is a small-molecule hedgehog signaling inhibitor selected under the group of benzimidazoles. In early research, benzimidazoles attracted large interest as they represented a class of inhibitors with low molecular weight, potent inhibitory activity, and lacking unstable functionality.1 The great lipophilicity of this group of compounds brought interest to further modification. This analysis concluded that the presence of p-cyano ureas presented good physicochemical and pharmacokinetic properties from which glasdegib was developed.1
Glasdegib was developed by Pfizer Inc and approved on November 21, 2018 by the FDA for the treatment of Acute Myeloid Leukemia (AML).11 Glasdegib targets cancerous cells by inhibiting the sonic hedgehog receptor smoothened (SMO), a transmembrane protein involved in the Hedgehog (Hh) signaling cascade.5 Aberrant of Hh signaling is one of the main pathophysiologies of AML, with observed overexpression or constitutive activation of SMO.6,7 Although the efficacy of glasdegib monotherapy is limited, the landmark Phase 2 Bright AML 1003 trial showed a superior overall survival and complete response when glasdegib is combined with low dose cytarabine. Currently, the current gold standard of AML in older patients is still venetoclax with hypomethylation agents, new clinical combinations of glasdegib are being tested in hope of replacing venetoclax due to glasdegib's more favorable side effects profile.5
- Accession Number
- DBSALT003035
- Structure
Structure for Glasdegib maleate (DBSALT003035)
- Synonyms
- Not Available
- UNII
- TH2EV99S4Z
- CAS Number
- 2030410-25-2
- Weight
- Average: 490.52
Monoisotopic: 490.196467961 - Chemical Formula
- C25H26N6O5
- InChI Key
- VJCVKWFBWAVYOC-UIXXXISESA-N
- InChI
- InChI=1S/C21H22N6O.C4H4O4/c1-27-11-10-16(24-21(28)23-15-8-6-14(13-22)7-9-15)12-19(27)20-25-17-4-2-3-5-18(17)26-20;5-3(6)1-2-4(7)8/h2-9,16,19H,10-12H2,1H3,(H,25,26)(H2,23,24,28);1-2H,(H,5,6)(H,7,8)/b;2-1-/t16-,19-;/m1./s1
- IUPAC Name
- (2Z)-but-2-enedioic acid; 1-[(2R,4R)-2-(1H-1,3-benzodiazol-2-yl)-1-methylpiperidin-4-yl]-3-(4-cyanophenyl)urea
- SMILES
- OC(=O)\C=C/C(O)=O.CN1CC[C@H](C[C@@H]1C1=NC2=CC=CC=C2N1)NC(=O)NC1=CC=C(C=C1)C#N
- External Links
- ChemSpider
- 58824299
- ChEMBL
- CHEMBL4297534
- Wikipedia
- Glasdegib
- Predicted Properties
Property Value Source Water Solubility 0.0469 mg/mL ALOGPS logP 2.68 ALOGPS logP 2.28 Chemaxon logS -3.9 ALOGPS pKa (Strongest Acidic) 11.39 Chemaxon pKa (Strongest Basic) 6.67 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 96.84 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 108.26 m3·mol-1 Chemaxon Polarizability 40.7 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon