Details of the Drug

General Information of Drug (ID: DMSB068)

Drug Name

PF-04449913

Synonyms

Glasdegib; 1095173-27-5; PF 04449913; UNII-K673DMO5H9; K673DMO5H9; CHEMBL2043437; Glasdegib (PF-04449913); Glasdegib [USAN:INN]; Glasdegib (USAN/INN); PF-04449913;Glasdegib; GTPL8201; Glasdegib(PF-04449913); EX-A858; MolPort-035-789-706; SFNSLLSYNZWZQG-VQIMIIECSA-N; ZINC68251434; PF-913; BDBM50385635; 2640AH; AKOS027324121; CS-2

Indication

Disease Entry	ICD 11	Status	REF
Chronic myelomonocytic leukaemia	2A40	Approved	[1]
Solid tumour/cancer	2A00-2F9Z	Approved	[2]

Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

374.4

Topological Polar Surface Area (xlogp)

2.4

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 9587 mcgh/L [3]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 321 mcg/L [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 4 h [3]
Bioavailability: The bioavailability of drug is 55% [3]
Clearance: The clearance of drug is 5.22 L/h [3]
Elimination: 49% is eliminated in the urine from which 17% is excreted as the unchanged form while 42% is eliminated in feces where 20% represents the unchanged form [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 17.4 hours [5]
Metabolism: The drug is metabolized via the CYP3A4 [4]
Vd: The volume of distribution (Vd) of drug is 225 L [3]

Chemical Identifiers

Formula: C21H22N6O
IUPAC Name: 1-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-3-(4-cyanophenyl)urea
Canonical SMILES: CN1CC[C@H](C[C@@H]1C2=NC3=CC=CC=C3N2)NC(=O)NC4=CC=C(C=C4)C#N
InChI: 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

Cross-matching ID

PubChem CID: 25166913
ChEBI ID: CHEBI:145428
CAS Number: 1095173-27-5
DrugBank ID: DB11978
TTD ID: D0S5LO
INTEDE ID: DR0774
ACDINA ID: D01126

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Hedgehog signaling pathway (HS pathway)	TT4LXBC	NOUNIPROTAC	Inhibitor	[1]
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[6]
Smoothened homolog (SMO)	TT8J1S3	SMO_HUMAN	Modulator	[7]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[8]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Substrate	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Chronic myelomonocytic leukaemia

ICD Disease Classification

2A40

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Serine/threonine-protein kinase mTOR (mTOR)	DTT	MTOR	2.16E-05	-0.44	-2.3
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	1.73E-04	1.53E-01	7.44E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from PF-04449913 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Major	Increased risk of prolong QT interval by the combination of PF-04449913 and Ivosidenib.	Acute myeloid leukaemia [2A60]	[37]
Gilteritinib	DMWQ4MZ	Moderate	Increased risk of prolong QT interval by the combination of PF-04449913 and Gilteritinib.	Acute myeloid leukaemia [2A60]	[38]
Oliceridine	DM6MDCF	Moderate	Increased risk of prolong QT interval by the combination of PF-04449913 and Oliceridine.	Acute pain [MG31]	[38]
Levalbuterol	DM5YBO1	Moderate	Increased risk of ventricular arrhythmias by the combination of PF-04449913 and Levalbuterol.	Asthma [CA23]	[39]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of PF-04449913 caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[38]
Pexidartinib	DMS2J0Z	Major	Increased metabolism of PF-04449913 caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[40]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of PF-04449913 caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[38]
Eslicarbazepine	DMZREFQ	Major	Increased metabolism of PF-04449913 caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[38]
Ripretinib	DM958QB	Moderate	Decreased clearance of PF-04449913 due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[41]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of PF-04449913 caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[38]
Brigatinib	DM7W94S	Moderate	Increased metabolism of PF-04449913 caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[38]
PF-06463922	DMKM7EW	Major	Increased metabolism of PF-04449913 caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[38]
Pralsetinib	DMWU0I2	Moderate	Decreased clearance of PF-04449913 due to the transporter inhibition by Pralsetinib.	Lung cancer [2C25]	[42]
Selpercatinib	DMZR15V	Major	Increased risk of prolong QT interval by the combination of PF-04449913 and Selpercatinib.	Lung cancer [2C25]	[43]
Ubrogepant	DM749I3	Moderate	Decreased clearance of PF-04449913 due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[42]
Rimegepant	DMHOAUG	Moderate	Decreased clearance of PF-04449913 due to the transporter inhibition by Rimegepant.	Migraine [8A80]	[44]
Siponimod	DM2R86O	Major	Increased risk of ventricular arrhythmias by the combination of PF-04449913 and Siponimod.	Multiple sclerosis [8A40]	[41]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of PF-04449913 and Ozanimod.	Multiple sclerosis [8A40]	[42]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of PF-04449913 caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[38]
Entrectinib	DMMPTLH	Moderate	Increased risk of prolong QT interval by the combination of PF-04449913 and Entrectinib.	Non-small cell lung cancer [2C25]	[38]
Rucaparib	DM9PVX8	Moderate	Increased risk of prolong QT interval by the combination of PF-04449913 and Rucaparib.	Ovarian cancer [2C73]	[38]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of PF-04449913 and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[45]
Lefamulin	DME6G97	Major	Increased risk of prolong QT interval by the combination of PF-04449913 and Lefamulin.	Pneumonia [CA40]	[46]
Darolutamide	DMV7YFT	Minor	Decreased clearance of PF-04449913 due to the transporter inhibition by Darolutamide.	Prostate cancer [2C82]	[47]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of PF-04449913 caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[38]
Telotristat ethyl	DMDIYFZ	Major	Increased metabolism of PF-04449913 caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[40]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of PF-04449913 caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[38]
Lusutrombopag	DMH6IKO	Moderate	Decreased clearance of PF-04449913 due to the transporter inhibition by Lusutrombopag.	Thrombocytopenia [3B64]	[48]
Elagolix	DMB2C0E	Moderate	Increased metabolism of PF-04449913 caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[38]
Betrixaban	DM2C4RF	Moderate	Decreased clearance of PF-04449913 due to the transporter inhibition by Betrixaban.	Venous thromboembolism [BD72]	[49]
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⏷ Show the Full List of 30 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Calcium hydrogenphosphate	E00294	24441	Diluent
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Hypromellose	E00634	Not Available	Coating agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
Haematite red	E00236	14833	Colorant
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 10 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Glasdegib 100 mg tablet	100 mg	Tablet	Oral
Glasdegib 25 mg tablet	25 mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

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