Drug Details

General Information of the Drug (ID: DR8583)
Name
Glasdegib
Synonyms
Glasdegib; 1095173-27-5; PF-04449913; PF 04449913; Glasdegib (PF-04449913); Daurismo; 1-((2R,4R)-2-(1H-benzo[d]iMidazol-2-yl)-1-Methylpiperidin-4-yl)-3-(4-cyanophenyl)urea; UNII-K673DMO5H9; 1-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-3-(4-cyanophenyl)urea; K673DMO5H9; CHEMBL2043437; C21H22N6O; PF-913; 1095173-27-5 (free base); PF-4449913; Glasdegib [USAN:INN]; glasdegibum; Glasdegib (USAN/INN); PF-04449913;Glasdegib; GTPL8201; SCHEMBL2068480; Glasdegib(PF-04449913); EX-A858; CHEBI:145428; AMY38164; 2640AH; BDBM50385635; MFCD25976839; NSC775772; ZINC68251434; CCG-268350; DB11978; NSC-775772; SB16679; NCGC00378600-02; BS-14357; HY-16391; QC-11459; S7160; D10636; Z-3230; J-690029; Q27077810; N-[(2R,4R)-2-(1H-Benzimidazol-2-yl)-1-methyl-4-piperidinyl]-N'-(4-cyanophenyl)urea; N-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-N'-(4-cyanophenyl)urea; 1-((2R,4R)-2-(1H-benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea(PF-04449913); 4-[(2R)-2-[(1R)-2,2,2-Trifluoro-1-hydroxyethyl]-1-pyrrolidinyl]-2-(trifluoromethyl)-benzonitrile
    Click to Show/Hide
Molecular Type
Small molecule
Disease Chronic myelomonocytic leukaemia [ICD-11: 2A40] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C21H22N6O
PubChem CID
25166913
Canonical SMILES
CN1CCC(CC1C2=NC3=CC=CC=C3N2)NC(=O)NC4=CC=C(C=C4)C#N
InChI
1S/C21H22N6O/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/h2-9,16,19H,10-12H2,1H3,(H,25,26)(H2,23,24,28)/t16-,19-/m1/s1
InChIKey
SFNSLLSYNZWZQG-VQIMIIECSA-N
CAS Number
CAS 1095173-27-5
ChEBI ID
CHEBI:145428
TTD Drug ID
D0S5LO
DrugBank ID
DB11978
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Daunorubicin      Streptomyces peucetius     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 Glasdegib plus cytarabine/daunorubicin was well tolerated and associated with clinical activity in patients with untreated AML or high-risk MDS.
Target and Pathway
Target(s) Serine/threonine-protein kinase mTOR (mTOR)  Molecule Info  [3]
Smoothened homolog (SMO)  Molecule Info  [4]
KEGG Pathway Hedgehog signaling pathway Click to Show/Hide
2 Pathways in cancer
3 Proteoglycans in cancer
4 Basal cell carcinoma
5 ErbB signaling pathway
6 HIF-1 signaling pathway
7 mTOR signaling pathway
8 PI3K-Akt signaling pathway
9 AMPK signaling pathway
10 Insulin signaling pathway
11 Thyroid hormone signaling pathway
12 Adipocytokine signaling pathway
13 Type II diabetes mellitus
14 MicroRNAs in cancer
15 Glioma
16 Prostate cancer
17 Acute myeloid leukemia
18 Central carbon metabolism in cancer
19 Choline metabolism in cancer
Panther Pathway Hedgehog signaling pathway Click to Show/Hide
2 Hypoxia response via HIF activation
3 Interleukin signaling pathway
Pathwhiz Pathway Leucine Stimulation on Insulin Signaling Click to Show/Hide
Pathway Interaction Database Signaling events mediated by the Hedgehog family Click to Show/Hide
2 Hedgehog signaling events mediated by Gli proteins
3 IL4-mediated signaling events
4 Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
5 IL12-mediated signaling events
6 CDC42 signaling events
7 LKB1 signaling events
8 Regulation of Telomerase
9 mTOR signaling pathway
10 CXCR4-mediated signaling events
11 EGFR-dependent Endothelin signaling events
12 IL2 signaling events mediated by PI3K
13 IFN-gamma pathway
14 ErbB1 downstream signaling
15 ErbB2/ErbB3 signaling events
16 CXCR3-mediated signaling events
17 Class I PI3K signaling events mediated by Akt
Reactome Class B/2 (Secretin family receptors) Click to Show/Hide
2 Hedgehog 'off' state
3 Activation of SMO
4 PIP3 activates AKT signaling
5 Macroautophagy
6 mTORC1-mediated signalling
7 HSF1-dependent transactivation
8 CD28 dependent PI3K/Akt signaling
9 VEGFR2 mediated vascular permeability
10 TP53 Regulates Metabolic Genes
11 Constitutive Signaling by AKT1 E17K in Cancer
WikiPathways Hedgehog Signaling Pathway Click to Show/Hide
2 Hair Follicle Development: Organogenesis (Part 2 of 3)
3 Hair Follicle Development: Induction (Part 1 of 3)
4 Integrated Pancreatic Cancer Pathway
5 GPCR ligand binding
6 GPCRs, Other
7 ErbB Signaling Pathway
8 Senescence and Autophagy in Cancer
9 Interferon type I signaling pathways
10 Insulin Signaling
11 EGF/EGFR Signaling Pathway
12 Wnt Signaling Pathway Netpath
13 Extracellular vesicle-mediated signaling in recipient cells
14 Cardiac Hypertrophic Response
15 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
16 PIP3 activates AKT signaling
17 Polycystic Kidney Disease Pathway
18 Alpha 6 Beta 4 signaling pathway
19 BDNF signaling pathway
20 Oncostatin M Signaling Pathway
21 Prostate Cancer
22 TSLP Signaling Pathway
23 FSH signaling pathway
24 Leptin signaling pathway
25 TSH signaling pathway
26 RANKL/RANK Signaling Pathway
27 SREBF and miR33 in cholesterol and lipid homeostasis
28 Integrated Breast Cancer Pathway
29 SREBP signalling
30 Signaling by Insulin receptor
31 Costimulation by the CD28 family
32 Type II diabetes mellitus
33 MicroRNAs in cardiomyocyte hypertrophy
34 TOR Signaling
35 AMPK Signaling
References
Reference 1 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
Reference 2 Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results. Am J Hematol. 2018 Nov;93(11):1301-1310.
Reference 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Reference 4 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
 Download Picture         KEGG Link