DEFACTINIB

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H21F3N8O3S
Molecular Weight	510.493
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CNC(=O)C1=CC=C(NC2=NC=C(C(NCC3=NC=CN=C3N(C)S(C)(=O)=O)=N2)C(F)(F)F)C=C1

InChI

InChIKey=FWLMVFUGMHIOAA-UHFFFAOYSA-N

InChI=1S/C20H21F3N8O3S/c1-24-18(32)12-4-6-13(7-5-12)29-19-28-10-14(20(21,22)23)16(30-19)27-11-15-17(26-9-8-25-15)31(2)35(3,33)34/h4-10H,11H2,1-3H3,(H,24,32)(H2,27,28,29,30)

HIDE SMILES / InChI

Molecular Formula	C20H21F3N8O3S
Molecular Weight	510.493
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

Defactinib is an oral, investigational drug candidate for the treatment of various solid tumors. Through dual inhibition of FAK and PYK2, defactinib targets key resistance mechanisms in the tumor microenvironment (TME), including limited local immune response, dense stroma, and resident cancer stem cells, that may limit the effectiveness of current and investigational treatments. Treatment-related adverse events are: unconjugated hyperbilirubinemia, fatigue and headache.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Focal adhesion kinase 1 15	Inhibitor 8,297		0.6 nM [IC50]
Protein tyrosine kinase 2 beta 3	Inhibitor 8,297		0.6 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Malignant pleural mesothelioma 11	Primary	Phase II 1,132	Unknown
Non small cell lung cancer 7	Primary	Phase II 1,132	Unknown
Ovarian cancer 157	Primary	Phase I 428	Unknown

C_max

Value	Dose	Analyte	Population
0.61 μg/mL	600 mg single, oral	DEFACTINIB serum	Homo sapiens
0.63 μg/mL	200 mg single, oral	DEFACTINIB serum	Homo sapiens
0.93 μg/mL	200 mg 2 times / day steady-state, oral	DEFACTINIB serum	Homo sapiens
0.96 μg/mL	400 mg 2 times / day steady-state, oral	DEFACTINIB serum	Homo sapiens
0.98 μg/mL	600 mg 2 times / day steady-state, oral	DEFACTINIB serum	Homo sapiens
596.5 ng/mL	300 mg single, oral	DEFACTINIB serum	Homo sapiens
356.8 ng/mL	750 mg single, oral	DEFACTINIB serum	Homo sapiens
436.9 ng/mL	500 mg single, oral	DEFACTINIB serum	Homo sapiens
295 ng/mL	300 mg single, oral	DEFACTINIB serum	Homo sapiens
184.4 ng/mL	200 mg single, oral	DEFACTINIB serum	Homo sapiens
75.4 ng/mL	100 mg single, oral	DEFACTINIB serum	Homo sapiens
93.1 ng/mL	50 mg single, oral	DEFACTINIB serum	Homo sapiens
7.8 ng/mL	25 mg single, oral	DEFACTINIB serum	Homo sapiens
7.7 ng/mL	12.5 mg single, oral	DEFACTINIB serum	Homo sapiens
552.6 ng/mL	425 mg single, oral	DEFACTINIB serum	Homo sapiens
603.2 ng/mL	425 mg single, oral	DEFACTINIB serum	Homo sapiens
0.67 μg/mL	400 mg single, oral	DEFACTINIB serum	Homo sapiens

AUC

Value	Dose	Analyte	Population
2.68 μg × h/mL	600 mg single, oral	DEFACTINIB serum	Homo sapiens
3.78 μg × h/mL	200 mg single, oral	DEFACTINIB serum	Homo sapiens
6.24 μg × h/mL	200 mg 2 times / day steady-state, oral	DEFACTINIB serum	Homo sapiens
5.71 μg × h/mL	400 mg 2 times / day steady-state, oral	DEFACTINIB serum	Homo sapiens
4.88 μg × h/mL	600 mg 2 times / day steady-state, oral	DEFACTINIB serum	Homo sapiens
3101 ng × h/mL	300 mg single, oral	DEFACTINIB serum	Homo sapiens
1737 ng × h/mL	750 mg single, oral	DEFACTINIB serum	Homo sapiens
1261 ng × h/mL	500 mg single, oral	DEFACTINIB serum	Homo sapiens
1400 ng × h/mL	300 mg single, oral	DEFACTINIB serum	Homo sapiens
632 ng × h/mL	200 mg single, oral	DEFACTINIB serum	Homo sapiens
340 ng × h/mL	100 mg single, oral	DEFACTINIB serum	Homo sapiens
357 ng × h/mL	50 mg single, oral	DEFACTINIB serum	Homo sapiens
47 ng × h/mL	25 mg single, oral	DEFACTINIB serum	Homo sapiens
32 ng × h/mL	12.5 mg single, oral	DEFACTINIB serum	Homo sapiens
6334.2 ng × h/mL	425 mg 2 times / day multiple, oral	DEFACTINIB serum	Homo sapiens
8372.7 ng × h/mL	300 mg 2 times / day multiple, oral	DEFACTINIB serum	Homo sapiens
2952.9 ng × h/mL	750 mg 2 times / day multiple, oral	DEFACTINIB serum	Homo sapiens
1639.3 ng × h/mL	500 mg 2 times / day multiple, oral	DEFACTINIB serum	Homo sapiens
25782.6 ng × h/mL	425 mg 2 times / day multiple, oral	DEFACTINIB serum	Homo sapiens
5180 ng × h/mL	300 mg 2 times / day multiple, oral	DEFACTINIB serum	Homo sapiens
2148.8 ng × h/mL	200 mg 2 times / day multiple, oral	DEFACTINIB serum	Homo sapiens
884 ng × h/mL	100 mg 2 times / day multiple, oral	DEFACTINIB serum	Homo sapiens
714 ng × h/mL	50 mg 2 times / day multiple, oral	DEFACTINIB serum	Homo sapiens
258.5 ng × h/mL	25 mg 2 times / day multiple, oral	DEFACTINIB serum	Homo sapiens
201.6 ng × h/mL	12.5 mg 2 times / day multiple, oral	DEFACTINIB serum	Homo sapiens
2658 ng × h/mL	425 mg single, oral	DEFACTINIB serum	Homo sapiens
3519 ng × h/mL	425 mg single, oral	DEFACTINIB serum	Homo sapiens
3.84 μg × h/mL	400 mg single, oral	DEFACTINIB serum	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
2.79 h	600 mg single, oral	DEFACTINIB serum	Homo sapiens
4.29 h	200 mg single, oral	DEFACTINIB serum	Homo sapiens
2.95 h	200 mg 2 times / day steady-state, oral	DEFACTINIB serum	Homo sapiens
2.95 h	400 mg 2 times / day steady-state, oral	DEFACTINIB serum	Homo sapiens
2.27 h	600 mg 2 times / day steady-state, oral	DEFACTINIB serum	Homo sapiens
8.6 h	300 mg single, oral	DEFACTINIB serum	Homo sapiens
11.1 h	750 mg single, oral	DEFACTINIB serum	Homo sapiens
7.8 h	500 mg single, oral	DEFACTINIB serum	Homo sapiens
9.2 h	300 mg single, oral	DEFACTINIB serum	Homo sapiens
2.1 h	200 mg single, oral	DEFACTINIB serum	Homo sapiens
11.7 h	100 mg single, oral	DEFACTINIB serum	Homo sapiens
5.6 h	50 mg single, oral	DEFACTINIB serum	Homo sapiens
3.8 h	12.5 mg single, oral	DEFACTINIB serum	Homo sapiens
8.9 h	425 mg single, oral	DEFACTINIB serum	Homo sapiens
6.5 h	425 mg single, oral	DEFACTINIB serum	Homo sapiens
2.45 h	400 mg single, oral	DEFACTINIB serum	Homo sapiens

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
001 Chemical	DY34250	https://www.001chemical.com/chem/search?q=DY34250
001 Chemical	DY34251	https://www.001chemical.com/chem/search?q=DY34251
1PlusChem LLC	1P008TW3	https://www.1pchem.com/search?query=1P008TW3
1PlusChem LLC	1P008U2E	https://www.1pchem.com/search?query=1P008U2E
Aceschem	ACF019970	https://www.aceschem.com/catalog/search.do?q=ACF019970

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PubMed

Show entries

Title	Date	PubMed
Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src.	1994 Mar	7509446
Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer.	1996 Jan	8770310