BELZUTIFAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H12F3NO4S
Molecular Weight	383.342
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CS(=O)(=O)C1=CC=C(OC2=CC(=CC(F)=C2)C#N)C3=C1[C@H](O)[C@H](F)[C@@H]3F

InChI

InChIKey=LOMMPXLFBTZENJ-ZACQAIPSSA-N

InChI=1S/C17H12F3NO4S/c1-26(23,24)12-3-2-11(13-14(12)17(22)16(20)15(13)19)25-10-5-8(7-21)4-9(18)6-10/h2-6,15-17,22H,1H3/t15-,16-,17+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C17H12F3NO4S
Molecular Weight	383.342
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215383s000lbl.pdf|https://pubmed.ncbi.nlm.nih.gov/34613603

Belzutifan (PT2977) is an orally active, small molecule inhibitor of hypoxia-inducible factor (HIF)-2alpha (HIF-2a). Upon oral administration, HIF-2alpha inhibitor PT2977 binds to and blocks the function of HIF-2alpha, thereby preventing HIF-2alpha heterodimerization and its subsequent binding to DNA. This results in decreased transcription and expression of HIF-2alpha downstream target genes, many of which regulate hypoxic signaling. This inhibits cell growth and survival of HIF-2alpha-expressing tumor cells. HIF-2alpha, the alpha subunit for the heterodimeric transcription factor HIF-2, is overexpressed in many cancers and promotes tumorigenesis.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Endothelial PAS domain-containing protein 1 7 Target ID: CHEMBL1744522 Sources: https://pubmed.ncbi.nlm.nih.gov/36167425\|https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215383s000lbl.pdf	Inhibitor 8504		9.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Advanced solid cancer 30 Sources: https://clinicaltrials.gov/ct2/show/NCT02974738	Primary	Phase I 438	Unknown Approved Use Unknown
Solid carcinoma 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02974738	Primary	Phase I 438	Unknown Approved Use Unknown
Clear cell adenocarcinoma 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02974738	Primary	Phase I 438	Unknown Approved Use Unknown
Renal cell carcinoma 33 Sources: https://clinicaltrials.gov/ct2/show/NCT02974738	Primary	Phase I 438	Unknown Approved Use Unknown
Von Hippel-Lindau disease 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215383s000lbl.pdf	Primary	Approved 8583	WELIREG Approved Use WELIREG is a hypoxia-inducible factor inhibitor indicated for treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. Launch Date 2021

C_max

Value	Dose	Analyte	Population
665 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf#page=244	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
1.3 μg/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215383s000lbl.pdf#page=9	120 mg 1 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
172.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
572 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1240.67 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1346 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	120 mg 1 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2042 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2540 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	240 mg 1 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1277 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	120 mg 2 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
245.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
540.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1402.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1791.98 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	120 mg 1 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2041.67 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2671.67 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	240 mg 1 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2672 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	120 mg 2 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
15 μg × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf#page=244	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
16.7 μg × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215383s000lbl.pdf#page=9	120 mg 1 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1530.59 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5396.19 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12513 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14559.56 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	120 mg 1 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16851.51 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
24767.93 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	240 mg 1 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8846.05 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	120 mg 2 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2170.64 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7136.85 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
18369.47 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21046.06 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	120 mg 1 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22271.92 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
27874.67 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	240 mg 1 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22256.03 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	120 mg 2 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
14 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215383s000lbl.pdf#page=9	120 mg 1 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
11.17 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.52 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
20.28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.84 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	120 mg 1 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.09 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.34 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	240 mg 1 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.49 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	120 mg 2 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12.87 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
18.52 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.48 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15.95 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	120 mg 1 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.18 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.88 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	240 mg 1 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.11 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33888901/ \| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128828/#SD1	120 mg 2 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BELZUTIFAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
55% OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf#page=41 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf#page=80			BELZUTIFAN plasma	Homo sapiens

Doses

Dose	Population	Adverse events
240 mg 1 times / day steady, oral Highest studied dose Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf	Disc. AE: Disease progression, Malignant neoplasm progression... AEs leading to discontinuation/dose reduction: Disease progression (1 patient) Malignant neoplasm progression (1 patient) Acute kidney injury (1 patient) Cardiac arrest (1 patient) Suicide (1 patient) Abdominal pain (1 patient) Fatigue (1 patient) Decreased appetite (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf
120 mg 1 times / day steady, oral Studied dose Dose: 120 mg, 1 times / day Route: oral Route: steady Dose: 120 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf	Disc. AE: Malignant neoplasm progression, Disease progression... AEs leading to discontinuation/dose reduction: Malignant neoplasm progression (1 patient) Disease progression (1 patient) Acute kidney injury (1 patient) Cardiac arrest (1 patient) Suicide (1 patient) Abdominal pain (1 patient) Fatigue (1 patient) Decreased appetite (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf
120 mg 1 times / day steady, oral Studied dose Dose: 120 mg, 1 times / day Route: oral Route: steady Dose: 120 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf	Disc. AE: Dizzines... AEs leading to discontinuation/dose reduction: Dizzines (Grade 1, 1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 substrate 1946 inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MATE2K 17 CYP2B6 926 BCRP 910 P-gp 1741 CYP2C19 2057 CYP2C8 1057 CYP1A2 2153 OATP1B3 961 OCT2 779 CYP3A5 136 OAT1 725 MATE1 415 OAT3 747 OATP1B1 1079	UGT2B17 237 CYP2C19 1119 P-gp 2052 OATP1B1 503 BCRP 697 OATP1B3 435	CYP2B6 669 CYP1A2 832

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
CYP3A5 201	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215383s000lbl.pdf Page: 10.0	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	no
MATE2K 17	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 81.0	yes
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 73 \| 81	yes	yes (co-administration study) Comment: Decreased midazolam AUC and Cmax by 40% and 34% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 73 \| 81

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT2B17 237	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 34 \| 40 \| 71 \| 73	major	yes (pharmacogenomic study) Comment: Based on popPK, UGT2B17, CYP2C19, or dual UGT2B17 and CYP2C19 poor metabolizer (PM) is predicted to have 2.0-, 1.6-, or 3.2-fold higher exposures (steady state AUC0-24hr), respectively, compared to a patient who is a UGT2B17 normal metabolizer (NM) and CYP2C19 non-poor (ultrarapid, rapid, normal, and intermediate) metabolizer. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 34 \| 40 \| 71 \| 73
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 40.0	minor
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 80.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 80 \| 92	weak
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 80 \| 92	weak
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 40 \| 92	weak
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 40 \| 71 \| 73	yes	yes (pharmacogenomic study) Comment: Based on popPK, UGT2B17, CYP2C19, or dual UGT2B17 and CYP2C19 poor metabolizer (PM) is predicted to have 2.0-, 1.6-, or 3.2-fold higher exposures (steady state AUC0-24hr), respectively, compared to a patient who is a UGT2B17 normal metabolizer (NM) and CYP2C19 non-poor (ultrarapid, rapid, normal, and intermediate) metabolizer. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 40 \| 71 \| 73

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215383Orig1s000MultidisciplineR.pdf Page: 33 \| 39

PubMed

Title	Date	PubMed
Belzutifan: a novel therapy for von Hippel-Lindau disease.	2022-04	35132216
Belzutifan: A Narrative Drug Review.	2022	35366789
Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease.	2021-11-25	34818478
Belzutifan: First Approval.	2021-11	34613603

Patents

Substance Class	Chemical Created by `admin` on `Wed Apr 02 08:50:57 GMT 2025` Edited by `admin` on `Wed Apr 02 08:50:57 GMT 2025`
Record UNII	7K28NB895L
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BELZUTIFAN

Official Name

English

belzutifan [INN]

Preferred Name

English

3-((1S,2S,3R)-2,3-DIFLUORO-1-HYDROXY-7-METHYLSULFONYLINDAN-4-YL)OXY-5-FLUORO-BENZONITRILE

Systematic Name

English

WELIREG

Brand Name

English

MK6482

Code

English

3-(((1S,2S,3R)-2,3-DIFLUORO-1-HYDROXY-7-(METHANESULFONYL)-2,3-DIHYDRO-1H-INDEN-4-YL)OXY)-5-FLUOROBENZONITRILE

Systematic Name

English

Belzutifan [WHO-DD]

Common Name

English

MK-6482

Code

English

BELZUTIFAN [ORANGE BOOK]

Common Name

English

PT-2977

Code

English

BENZONITRILE, 3-(((1S,2S,3R)-2,3-DIFLUORO-2,3-DIHYDRO-1-HYDROXY-7-(METHYLSULFONYL)-1H-INDEN-4-YL)OXY)-5-FLUORO-

Systematic Name

English

PT2977

Code

English

BELZUTIFAN [USAN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

745820