FEDRATINIB HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H36N6O3S.2ClH.H2O
Molecular Weight	615.615
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.Cl.Cl.CC1=CN=C(NC2=CC=C(OCCN3CCCC3)C=C2)N=C1NC4=CC=CC(=C4)S(=O)(=O)NC(C)(C)C

InChI

InChIKey=QAFZLTVOFJHYDF-UHFFFAOYSA-N

InChI=1S/C27H36N6O3S.2ClH.H2O/c1-20-19-28-26(30-21-10-12-23(13-11-21)36-17-16-33-14-5-6-15-33)31-25(20)29-22-8-7-9-24(18-22)37(34,35)32-27(2,3)4;;;/h7-13,18-19,32H,5-6,14-17H2,1-4H3,(H2,28,29,30,31);2*1H;1H2

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

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

Molecular Formula	C27H36N6O3S
Molecular Weight	524.678
Charge	0
Count

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

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18394554
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26181658 | http://adisinsight.springer.com/drugs/800027763

Fedratinib (SAR-302503, TG-101348) is a selective small-molecule inhibitor of Janus kinase-2. Fedratinib demonstrated therapeutic efficacy in a murine model of myeloproliferative disease. Sanofi was developing Fedratinib for the treatment of myeloproliferative diseases and solid tumors. The clinical development of fedratinib was terminated after reports of Wernicke's encephalopathy in myelofibrosis patients.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase JAK2 55 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18394554	Inhibitor 8297		3.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Polycythemia vera 15 Sources: http://adisinsight.springer.com/drugs/800027763 https://www.ncbi.nlm.nih.gov/pubmed/18394554	Primary	Phase II 1132	Unknown Approved Use Unknown
Myelofibrosis 15 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26181658 http://adisinsight.springer.com/drugs/800027763	Primary	Phase II 1132	Unknown Approved Use Unknown
Solid tumors 145 Sources: http://adisinsight.springer.com/drugs/800027763	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1804 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FEDRATINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2539 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FEDRATINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1760 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24165976	680 mg single, oral dose: 680 mg route of administration: Oral experiment type: SINGLE co-administered:	FEDRATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
26870 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FEDRATINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
38712 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FEDRATINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
17800 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24165976	680 mg single, oral dose: 680 mg route of administration: Oral experiment type: SINGLE co-administered:	FEDRATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
41 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		FEDRATINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
62.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24165976	680 mg single, oral dose: 680 mg route of administration: Oral experiment type: SINGLE co-administered:		FEDRATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Analyte	Population
8% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FEDRATINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FEDRATINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
8% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf		FEDRATINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf Page: 6.1	unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf Page: 6.1	Disc. AE: Nausea, Cardiac failure... Other AEs: Diarrhea, Nausea... AEs leading to discontinuation/dose reduction: Nausea (>3) Cardiac failure (grade 3-4, 3%) Cardiac failure (grade 5, 1%) Thrombocytopenia (2%) Myocardial ischemia (2%) Diarrhea (2%) Blood creatinine increased (2%) Other AEs: Diarrhea (>3) Nausea (>3) Anemia (6%) Diarrhea (3%) Vomiting (3%) Thrombocytopenia (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf Page: 6.1
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf Page: Table 3	unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf Page: Table 3	Other AEs: Diarrhea, Nausea... Other AEs: Diarrhea (all grades, 66%) Nausea (all grades, 62%) Anemia (all grades, 40%) Vomiting (all grades, 39%) Asthenia (all grades, 19%) Muscle spasms (all grades, 12%) Blood creatinine increased (all grades, 10%) Pain in extremity (all grades, 10%) Alanine aminotransferase increased (all grades, 9%) Headache (all grades, 9%) Weight increased (all grades, 9%) Dizziness (all grades, 8%) Bone pain (all grades, 8%) Urinary tract infection (all grades, 6%) Dysuria (all grades, 6%) Aspartate aminotransferase increased (all grades, 5%) Diarrhea (grade 3-4, 5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf Page: Table 3
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf Page: Table 4	unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf Page: Table 4	Other AEs: Anemia, Vomiting... Other AEs: Anemia (grade 3-4, 30%) Vomiting (grade 3-4, 3.1%) Asthenia (grade 3-4, 5%) Blood creatinine increased (grade 3-4, 1%) Thrombocytopenia (all grades, 47%) Neutropenia (all grades, 23%) Lipase increased (all grades, 35%) Hyponatremia (all grades, 26%) Amylase increased (all grades, 24%) Thrombocytopenia (grade 3-4, 12%) Neutropenia (grade 3-4, 5%) Lipase increased (grade 3-4, 10%) Hyponatremia (grade 3-4, 5%) Amylase increased (grade 3-4, 2.1%) Cardiac failure (all grades, 5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf Page: Table 4
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis \| post-polycythemia vera myelofibrosis \| post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Sex: M+F Population Size: 97 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	Disc. AE: Anemia... AEs leading to discontinuation/dose reduction: Anemia (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf Page: 123	unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis \| post-polycythemia vera myelofibrosis \| post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Sex: M+F Population Size: 97 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf Page: 123	Disc. AE: Cardiac disorders... AEs leading to discontinuation/dose reduction: Cardiac disorders (grade 5, 2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf Page: 123
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis \| post-polycythemia vera myelofibrosis \| post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	Disc. AE: Thrombocytopenia, Neutropenia... AEs leading to discontinuation/dose reduction: Thrombocytopenia (6%) Neutropenia (2%) Vomiting (4%) Blood creatinine increased (2%) Diarrhea (2%) Nausea (2%) Amylase increased (1%) Lipase increased (3%) Fatigue (2%) Diarrhea (all grades, 8%) Diarrhea (grade 3-4, 3%) Nausea (all grades, 6%) Nausea (grade 3-4, 4%) Vomiting (all grades, 11%) Vomiting (grade 3-4, 7%) Anemia (all grades, 18%) Anemia (grade 3-4, 14%) Thrombocytopenia (all grades, 7%) Thrombocytopenia (grade 3-4, 6%) Fatigue (all grades, 5%) Fatigue (grade 3-4, 5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis \| post-polycythemia vera myelofibrosis \| post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	Disc. AE: Anemia, Diarrhea... AEs leading to discontinuation/dose reduction: Anemia (2%) Diarrhea (2%) Nausea (2%) Amylase increased (1%) Lipase increased (1%) Vomiting (all grades, 10%) Vomiting (grade 3-4, 3%) Anemia (all grades, 8%) Anemia (grade 3-4, 5%) Thrombocytopenia (all grades, 3%) Thrombocytopenia (grade 3-4, 2%) Fatigue (all grades, 3%) Fatigue (grade 3-4, 3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf Page: 123	unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf Page: 123	Disc. AE: Cardiac disorders... AEs leading to discontinuation/dose reduction: Cardiac disorders (grade 5, 2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf Page: 123
800 mg single, oral Highest studied dose Dose: 800 mg Route: oral Route: single Dose: 800 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf Page: 20	unhealthy, adult n = 1 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: unknown Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf Page: 20	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf Page: 20
680 mg 1 times / day multiple, oral MTD Dose: 680 mg, 1 times / day Route: oral Route: multiple Dose: 680 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf Page: 68	unhealthy, adult n = 31 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: unknown Population Size: 31 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf Page: 68	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf Page: 68
680 mg single, oral MTD Dose: 680 mg Route: oral Route: single Dose: 680 mg Sources: https://pubmed.ncbi.nlm.nih.gov/24165976/	healthy, adult n = 2 Health Status: healthy Age Group: adult Sex: M Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/24165976/	Other AEs: Gastrointestinal disorders... Other AEs: Gastrointestinal disorders Sources: https://pubmed.ncbi.nlm.nih.gov/24165976/
800 mg 1 times / day multiple, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	unhealthy n = 6 Health Status: unhealthy Population Size: 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699 MATE1 306 MATE2 263 OCT2 647 OATP1B1 788 OATP1B3 706 OAT1 599 OAT3 642 OCT1 512 CYP2C19 1478 CYP1A2 1524 CYP2B6 810 CYP2C8 911	P-gp 1537 CYP2C19 991 FMO3 67 BCRP 561 OATP1B1 406 OATP1B3 350 BSEP 52 MRP2 205	CYP3A 129

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	no
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	no
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes [IC50 0.227 uM]
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes [IC50 0.352 uM]
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes [IC50 0.78 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes [IC50 10.1 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes [IC50 100.8 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes [IC50 16.4 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes [IC50 20.2 uM]	yes (co-administration study) Comment: fedratinib increased exposure of metoprolol by 2x Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes [IC50 29.9 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes [IC50 3 uM]	yes (co-administration study) Comment: fedratinib increased exposure of midazolam by 4x Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes [IC50 52.2 uM]
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes [IC50 6.06 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes [IC50 9.51 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes	yes (co-administration study) Comment: fedratinib increased exposure of omeprazole by 3x Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	major
FMO3 67	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	major
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	major	yes (co-administration study) Comment: ketoconazole increased cmax of fedratinib by 4x Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	no
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	no
MRP2 205	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212327Orig1s000MultidisciplineR.pdf

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY443054	https://www.001chemical.com/chem/936091-26-8
AA Blocks	AA00GU48	https://www.aablocks.com/goods/Goods/detail?id=AA00GU48
AK Scientific, Inc. (AKSCI)	SYN1104	http://www.aksci.com/item_detail.php?cat=SYN1104
AK Scientific, Inc. (AKSCI)	Y0268	http://www.aksci.com/item_detail.php?cat=Y0268
Aaron Chemicals	AR00GUW0	http://www.aaronchem.com/936091-26-8
AbMole Bioscience	1733	http://www.abmole.com/product.asp?id=1733
AbMole Bioscience	M1733	http://www.abmole.com/products/tg101348.html
Acadechem	ACDX-011122	http://acadechemical.com/product/86010
Aceschem	ACS019922	https://www.aceschem.com/catalog/936091-26-8.html
Achemtek	0101-002350	http://www.achemtek.com/936091-26-8
Active Biopharma	ABP000705	http://www.activebiopharma.com/936091-26-8
Adooq BioScience	TG-101348	http://www.adooq.com/tg-101348.html
Adooq BioScience	A11082	https://www.adooq.com/tg-101348.html
Allbio Pharm Co., Ltd	AD00400	http://www.allbiopharm.com/product/n/AD00400
Alsachim	4373	http://www.alsachim.com/product-C5698-glo.bal-view.html
Ambeed	A345883	https://www.ambeed.com/products/936091-26-8.html
Ambinter	Amb22169887	http://www.ambinter.com/reference/22169887
Angel Pharmatech	AG-10380	http://www.angelpharmatech.com/936091-26-8.html
ApexBio Technology	A4136	http://www.apexbt.com/tg101348-sar302503.html
Ark Pharm	AK-50248	http://www.arkpharminc.com/products/936091-26-8.html
Ark Pharma Scientific Limited	A-0185	http://www.arkpharmtech.com/product/32136.html
Aurora Fine Chemicals LLC	K16.642.248	http://online.aurorafinechemicals.com/info?ID=K16.642.248
Aurum Pharmatech LLC	W-5547	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5547
Axon MedChem	1588	https://www.axonmedchem.com/product/1588
BLD Pharm	BD166858	http://www.bldpharm.com/products/936091-26-8.html
BOC Sciences	936091-26-8	https://www.bocsci.com/fedratinib-cas-936091-26-8-item-100796.html
BioChemPartner	BCP02300	http://www.biochempartner.com/936091-26-8-BCP02300
BioCrick	BCC2190	http://www.biocrick.com/TG101348-SAR302503-BCC2190.html
BioSynth	J-523769	https://www.biosynth.com/en/products/all-products/products/J-523769.html
Boerchem	BC644857	http://www.boerchem.com/?product_41978.html
CSNpharm	CSN12405	https://www.csnpharm.com/products/tg-101348.html
Chem Scene	CS-0052	http://www.chemscene.com/936091-26-8.html
ChemMol	44022659	http://www.chemmol.com/chemmol/44022659.html
ChemieTek	CT-TG101	http://www.chemietek.com/tg101348-details.aspx
Chemspace	CSSB00015190596	https://chem-space.com/CSSB00015190596
DC Chemicals	DC7318	http://www.dcchemicals.com/product_show-TG101348_Fedratinib_.html
Debye Scientific	DB-079623	http://www.debyesci.com/cas_936091-26-8.html
Debye Scientific	DA-40258	http://www.debyesci.com/cas_945381-69-1.html
Excenen	EX-A170	http://www.excenen.com/searchresultlist.php?id=936091-26-8
Finetech	FT-0705969	http://www.finetechnology-ind.com/prod/detail/pub/1374744-69-0.html
Finetech	FT-0766818	http://www.finetechnology-ind.com/prod/detail/pub/936091-26-8.html
Finetech	FT-0763396	http://www.finetechnology-ind.com/prod/detail/pub/945381-69-1.html
Hairui	HR33073	http://www.hairuichem.com/en/product/936091-26-8.html
Huateng Pharma	F92627	https://en.huatengsci.com/products/intermediates/
Lab Network	LN01308311	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01308311
Matrix Scientific	147234	https://www.matrixscientific.com/147234.html
MedChem Express	HY-10409	https://www.medchemexpress.com/TG-101348.html
Molcore	MC443054	https://www.molcore.com/product/936091-26-8
OChem	29958	http://www.ocheminc.com/index.php?act=psearch&pid=091D268
Renno Tech	RS0112	http://www.rennotech.com/product_show.asp?id=35712
Smolecule	S547874	http://www.smolecule.com/products/s547874
Smolecule	S766760	https://www.smolecule.com/products/s766760
Synblock Inc	SB14604	http://www.synblock.com/product/936091-26-8.html
THE BioTek	bt-287151	https://www.thebiotek.com/product/inhibitors/bt-287151
THE BioTek	bt-504588	https://www.thebiotek.com/product/others/bt-504588
VladaChem	VL279311-100MG	https://www.vladachem.com/product.php?products=936091-26-8
Yuhao Chemical	YH65945	http://chemyuhao.com/936091-26-8.html
abcr GmbH	AB482480	http://www.abcr.com/shop/en/AB482480
eNovation Chemicals	D320287	https://www.enovationchem.com/ProductDetails.asp?ProductID=D320287
eNovation Chemicals	K31297	https://www.enovationchem.com/ProductDetails.asp?ProductID=K31297
eNovation Chemicals	Y0973935	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0973935
iChemical	EBD8909	http://www.ichemical.com/chemicals/cas-936091-26-8

PubMed

Title	Date	PubMed
		252160278
Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3.	2010 Dec 15	21106455
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010 Nov 24	21095574
Comprehensive analysis of kinase inhibitor selectivity.	2011 Oct 30	22037378
Dual kinase-bromodomain inhibitors for rationally designed polypharmacology.	2014 Apr	24584101
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs.	2015 Jun	25752796

Patents

Sample Use Guides

In Vivo Use Guide

Fedratinib therapy in patients with primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF: once-daily oral fedratinib, at a dose of 400 mg or 500 mg, or placebo, for at least 6 consecutive 4-week cycles. Fedratinib therapy significantly reduced splenomegaly and symptom burden in patients with MF. These benefits were accompanied by toxic effects in some patients, the most important being encephalopathy of unknown mechanism. Clinical development of fedratinib was subsequently discontinued.

Route of Administration: Oral

In Vitro Use Guide

300 nM Fedratinib (SAR-302503, TG-101348) significantly inhibited JAK2V617F+ progenitor-derived colony formation

Substance Class	Chemical Created by `admin` on `Sat Dec 16 00:40:42 GMT 2023` Edited by `admin` on `Sat Dec 16 00:40:42 GMT 2023`
Record UNII	UH9J2HBQWJ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FEDRATINIB HYDROCHLORIDE

Official Name

English

Fedratinib dihydrochloride monohydrate [WHO-DD]

Common Name

English

N-TERT-BUTYL-3-((5-METHYL-2-((4-(2-PYRROLIDIN-1-YLETHOXY)PHENYL)AMINO)PYRIMIDIN-4-YL)AMINO) BENZENESULFONAMIDE DIHYDROCHLORIDE MONOHYDRATE

Systematic Name

English

FEDRATINIB DIHYDROCHLORIDE MONOHYDRATE

Common Name

English

FEDRATINIB HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

INREBIC

Brand Name

English

SAR302503A

Code

English

FEDRATINIB HYDROCHLORIDE MONOHYDRATE [MI]

Common Name

English

BENZENESULFONAMIDE, N-(1,1-DIMETHYLETHYL)-3-((5-METHYL-2-((4-(2-(1-PYRROLIDINYL)ETHOXY)PHENYL)AMINO)-4-PYRIMIDINYL)AMINO)-, HYDROCHLORIDE, HYDRATE (1:2:1)

Systematic Name

English

FEDRATINIB HYDROCHLORIDE [USAN]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/10/811