DONAFENIB

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H16ClF3N4O3
Molecular Weight	467.843
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

[2H]C([2H])([2H])NC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1

InChI

InChIKey=MLDQJTXFUGDVEO-FIBGUPNXSA-N

InChI=1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31)/i1D3

HIDE SMILES / InChI

Molecular Formula	C21H16ClF3N4O3
Molecular Weight	467.843
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Donafenib (CM-4307) is a derivative of sorafenib, where [1H] hydrogens on the terminal methyl group are substituted by deuterium. The drug was developed by the Chinese company Suzhou Zelgen Biopharmaceuticals. Upon oral administration, donafenib binds to and blocks the activity of Raf kinase, and inhibits Raf-mediated signal transduction pathways. This inhibits cell proliferation in Raf-expressing tumor cells. In addition, donafenib may inhibit unidentified RTKs, and thus may further block tumor cell proliferation in susceptible tumor cells. Donafenib is being investigated in phase 3 clinical trials for the treatment of 131I-refractory differentiated thyroid cancer, advanced hepatocellular carcinoma, and metastatic colorectal cancer.

Originator

Approval Year

C_max

Value	Dose	Analyte	Population
0.395 μg/mL	100 mg single, oral	CM-4307 plasma	Homo sapiens
1.77 μg/mL	200 mg single, oral	CM-4307 plasma	Homo sapiens
1.68 μg/mL	300 mg single, oral	CM-4307 plasma	Homo sapiens
2.58 μg/mL	400 mg single, oral	CM-4307 plasma	Homo sapiens
4.94 μg/mL	100 mg 2 times / day multiple, oral	CM-4307 plasma	Homo sapiens
7.02 μg/mL	200 mg 2 times / day multiple, oral	CM-4307 plasma	Homo sapiens
6.95 μg/mL	300 mg 2 times / day multiple, oral	CM-4307 plasma	Homo sapiens
7.34 μg/mL	400 mg 2 times / day multiple, oral	CM-4307 plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
14.5 μg × h/mL	100 mg single, oral	CM-4307 plasma	Homo sapiens
54.1 μg × h/mL	200 mg single, oral	CM-4307 plasma	Homo sapiens
62.3 μg × h/mL	300 mg single, oral	CM-4307 plasma	Homo sapiens
102 μg × h/mL	400 mg single, oral	CM-4307 plasma	Homo sapiens
40.6 μg × h/mL	100 mg 2 times / day multiple, oral	CM-4307 plasma	Homo sapiens
44 μg × h/mL	200 mg 2 times / day multiple, oral	CM-4307 plasma	Homo sapiens
41.5 μg × h/mL	300 mg 2 times / day multiple, oral	CM-4307 plasma	Homo sapiens
49.1 μg × h/mL	400 mg 2 times / day multiple, oral	CM-4307 plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
23.9 h	100 mg single, oral	CM-4307 plasma	Homo sapiens
20.7 h	200 mg single, oral	CM-4307 plasma	Homo sapiens
27.8 h	300 mg single, oral	CM-4307 plasma	Homo sapiens
22.8 h	400 mg single, oral	CM-4307 plasma	Homo sapiens

Substance Class	Chemical
Record UNII	41XGO0VS1U
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

DONAFENIB

Common Name

English

4-(4-((((4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)AMINO)CARBONYL)AMINO)PHENOXY)-N-(METHYL-D3)-2-PYRIDINECARBOXAMIDE

Systematic Name

English

CM-4307

Code

English

Donafenib [WHO-DD]

Common Name

English

2-PYRIDINECARBOXAMIDE, 4-(4-((((4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)AMINO)CARBONYL)AMINO)PHENOXY)-N-(METHYL-D3)-

Systematic Name

English

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Classification Tree

Code System

Code

Antineoplastic Protein Inhibitor

NCI_THESAURUS

C129825

Serine/Threonine Kinase Inhibitor

NCI_THESAURUS

C2336

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Code System

Code

Type

Description

CAS

1130115-44-4

PRIMARY

PUBCHEM

25191001

PRIMARY

SMS_ID

100000183796

PRIMARY

NCI_THESAURUS

C118294

PRIMARY

DRUG BANK

DB15414

PRIMARY

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Related Record

Type

Details


					F3C1QUT2IS

DONAFENIB MESYLATE

SALT/SOLVATE -> PARENT

Amount:

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Related Record

Type

Details


					41XGO0VS1U

DONAFENIB

ACTIVE MOIETY

Comments:

Official Title: Efficacy and Safety of Donafenib in Patients With Advanced Hepatocellular Carcinoma: a Controlled,Multicentre,Randomised, Phase 3 Trial Purpose: Donafenib versus sorafenib for advanced hepatocellular cancer.


					41XGO0VS1U

DONAFENIB

ACTIVE MOIETY

Comments:

Drug: Donafenib(Primary); Indication: Colorectal cancer; Focus: Adverse reactions; Sponsor: Suzhou Zelgen Biopharmaceuticals; Most Recent Events: 04 Jan 2016 Status changed from recruiting to completed, as reported by ClinicalTrials.gov., 07 Jul 2015 New trial record

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SMILES

InChI

Originator

Approval Year

Cmax

AUC

T1/2

C_max

T_1/2