TECOVIRIMAT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H15F3N2O3
Molecular Weight	376.3292
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

[H][C@@]12C[C@]1([H])[C@@H]3C=C[C@H]2[C@@]4([H])C(=O)N(NC(=O)C5=CC=C(C=C5)C(F)(F)F)C(=O)[C@@]34[H]

InChI

InChIKey=CSKDFZIMJXRJGH-VWLPUNTISA-N

InChI=1S/C19H15F3N2O3/c20-19(21,22)9-3-1-8(2-4-9)16(25)23-24-17(26)14-10-5-6-11(13-7-12(10)13)15(14)18(24)27/h1-6,10-15H,7H2,(H,23,25)/t10-,11+,12+,13-,14-,15+

HIDE SMILES / InChI

Molecular Formula	C19H15F3N2O3
Molecular Weight	376.3292
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Tecovirimat (ST-246) is a low-molecular-weight compound (molecular weight = 376), that is potent (concentration that inhibited virus replication by 50% = 0.010 microM), selective (concentration of compound that inhibited cell viability by 50% = >40 microM), and active against multiple orthopoxviruses, including vaccinia, monkeypox, camelpox, cowpox, ectromelia (mousepox), and variola viruses. The antiviral activity is specific for orthopoxviruses and the compound does not inhibit the replication of other RNA- and DNA-containing viruses or inhibit cell proliferation at concentrations of compound that are antiviral. ST-246 targets vaccinia virus p37, a viral protein required for envelopment and secretion of extracellular forms of virus. The compound is orally bioavailable and protects multiple animal species from lethal orthopoxvirus challenge. rug substance and drug product processes have been developed and commercial scale batches have been produced using Good Manufacturing Processes (GMP). Human phase I clinical trials have shown that ST-246 is safe and well tolerated in healthy human volunteers. Based on the results of the clinical evaluation, once a day dosing should provide plasma drug exposure in the range predicted to be antiviral based on data from efficacy studies in animal models of orthopoxvirus disease.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
temporal expression: late 2	Inhibitor 8,297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Human smallpox disease 2	Curative		Approved 8,429	TPOXX

C_max

Value	Dose	Analyte	Population
1591 ng/mL	600 mg single, oral	TECOVIRIMAT plasma	Homo sapiens
2106 ng/mL	600 mg 2 times / day steady-state, oral	TECOVIRIMAT plasma	Homo sapiens
2209 ng/mL	600 mg 2 times / day steady-state, oral	TECOVIRIMAT plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
25876 ng × h/mL	600 mg single, oral	TECOVIRIMAT plasma	Homo sapiens
28791 ng × h/mL	600 mg 2 times / day steady-state, oral	TECOVIRIMAT plasma	Homo sapiens
30632 ng × h/mL	600 mg 2 times / day steady-state, oral	TECOVIRIMAT plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
20 h	600 mg 2 times / day steady-state, oral		TECOVIRIMAT plasma	Homo sapiens
23 h	600 mg 2 times / day steady-state, oral		TECOVIRIMAT plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
20.5%	600 mg 2 times / day steady-state, oral		TECOVIRIMAT plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
600 mg 2 times / day steady, oral Recommended	healthy, 18-79 years n = 359	Disc. AE: Abnormal EEG, Upset stomach... Other AEs: Headache, Nausea...
600 mg 2 times / day steady, oral Recommended	healthy, 18-79 years n = 359	Disc. AE: Arthralgia, Osteoarthritis...
600 mg 2 times / day steady, oral Recommended	healthy, 18-79 years n = 359	Disc. AE: Abnormal EEG, Abdominal discomfort...
2000 mg single, oral Highest studied dose	healthy, 30-33 years n = 7
1000 mg single, oral Recommended	healthy, 30-33 years n = 8	Other AEs: Neutropenia, Constipation...

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AEs

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AE	Significance	Dose	Population
Headache	12%	600 mg 2 times / day steady, oral Recommended	healthy, 18-79 years n = 359
Abdominal pain	2%	600 mg 2 times / day steady, oral Recommended	healthy, 18-79 years n = 359
Vomiting	2%	600 mg 2 times / day steady, oral Recommended	healthy, 18-79 years n = 359
Abnormal EEG	2% Disc. AE	600 mg 2 times / day steady, oral Recommended	healthy, 18-79 years n = 359
Chills	2% Disc. AE	600 mg 2 times / day steady, oral Recommended	healthy, 18-79 years n = 359

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737 inhibitor 1,587	inducer 389 substrate 1,037 inhibitor 1,767	substrate 1,217 inhibitor 1,852	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP2C19 1,478 CYP1A2 1,524 CYP2A6 707 CYP2B6 810 CYP2E1 882 P-gp 1,461 OATP1B1 788 OATP1B3 706 OAT1 599 OAT3 642 OCT2 647 BCRP 699	UGT1A1 418 UGT1A4 347 P-gp 1,537 BCRP 561 CYP1A2 1,054 CYP2B6 664 CYP2C8 693 CYP2C19 991 OATP1B1 406 OATP1B3 350 UGT1A3 422	CYP2B6 547 CYP3A 129

Drug as perpetrator

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Target	Modality	Activity
CYP1A2 1,692	inhibitor 3,277	no
CYP2A6 739	inhibitor 3,277	no
CYP2B6 1,001	inhibitor 3,277	no
CYP2D6 1,891	inhibitor 3,277	no
CYP2E1 970	inhibitor 3,277	no

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Drug as victim

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Target	Modality	Activity
BCRP 561	substrate 3,367	no
CYP1A2 1,054	substrate 3,367	no
CYP2B6 664	substrate 3,367	no
CYP2C19 991	substrate 3,367	no
CYP2C8 693	substrate 3,367	no

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
AN PharmaTech	AN-27268
Ambinter	Amb24076326	http://www.ambinter.com/reference/24076326
ApexBio Technology	B4829	http://www.apexbt.com/tecovirimat.html
BOC Sciences	816458-31-8
BioCrick	BCC5518	http://www.biocrick.com/Tecovirimat-BCC5518.html

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PubMed

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Title	Date	PubMed
An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus Challenge.	2005 Oct	16189015
Tricyclononene carboxamide derivatives as novel anti-HIV-1 agents.	2010 Sep	20598780

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Patents

Sample Use Guides

In Vivo Use Guide

Phase 2, double-blind, randomized, placebo-controlled, multicenter trial was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of tecovirimat (ST-246) when administered as a single daily oral dose (400 mg or 600 mg) for 14 days in fed adult volunteers.

Route of Administration: Oral

In Vitro Use Guide

BSC-40 cells were infected with 2 PFU/cell of vaccinia virus and incubated in the presence and absence of 5 uM tecovirimat (ST-246) . At selected times postinfection, extracellular virus in the medium and cell associated virus were quantified by plaque assay. The results show that ST-246 reduced extracellular virus titers by approximately 10 fold at 24 h postinfection, while having little effect on the level of intracellular virus titers relative to untreated controls. These results suggest that ST-246 inhibits extracellular virus formation.

Substance Class	Chemical
Record UNII	F925RR824R
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

TECOVIRIMAT

Official Name

English

tecovirimat [INN]

Common Name

English

TECOVIRIMAT [USAN]

Common Name

English

BENZAMIDE, N-((3AR,4R,4AR,5AS,6S,6AS)-3,3A,4,4A,5,5A,6,6A-OCTAHYDRO-1,3-DIOXO-4,6-ETHENOCYCLOPROP(F)ISOINDOL-2(1H)-YL)-4-(TRIFLUOROMETHYL)-, REL-

Common Name

English

Tecovirimat [WHO-DD]

Common Name

English

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Classification Tree

Code System

Code

Anti-Infective Agent

NCI_THESAURUS

C281

Designated

FDA ORPHAN DRUG

316210

Designated/Approved

FDA ORPHAN DRUG

229806

Designated

FDA ORPHAN DRUG

233506

Withdrawn

EU-Orphan Drug

EU/3/10/799

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Code System

Code

Type

Description

FDA UNII

F925RR824R

PRIMARY

MESH

C505045

PRIMARY

SMS_ID

100000177253

PRIMARY

USAN

TT-70

PRIMARY

DRUG BANK

DB12020

PRIMARY

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Related Record

Type

Details


					SB96YO2BR8

TECOVIRIMAT MONOHYDRATE

SOLVATE->ANHYDROUS

Amount:


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:

80 % [77 to 82] (average)


					K8F27CYD58

Monkeypox virus

TARGET ORGANISM->INHIBITOR

Comments:

Highly active against an MPXV strain MPXV/France/ IRBA2211i/2022 that was isolated from a patient in France during the 2022 monkeypox outbreak.

Amount:

12.7 NANOMOLAR (average)


					081I12ZA58

CYTOCHROME P450 2C19

METABOLIC ENZYME -> INHIBITOR

Interaction Type:

MINOR

Amount:


					JDS6958QAG

VACCINIA VIRUS

TARGET ORGANISM->INHIBITOR

Qualification:

EC50

Amount:

9 NANOMOLAR (average)

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Related Record

Type

Details


					KA05X8S21Z

4-TRIFLUOROMETHYL BENZOIC ACID

METABOLITE INACTIVE -> PARENT

Interaction Type:

MAJOR

Amount:


					FHP4KNX5CA

4,6-ETHENOCYCLOPROP(F)ISOINDOLE-1,3(2H,3AH)-DIONE, 4,4A,5,5A,6,6A-HEXAHYDRO-, (3A.ALPHA.,4.BETA.,4A.ALPHA.,5A.ALPHA.,6.BETA.,6A.ALPHA.)-

METABOLITE INACTIVE -> PARENT

Amount:


					57LY3IKN0N

2-AMINO-4,4A,5,5A,6,6A-HEXAHYDRO-4,6-ETHENOCYCLOPROP(F)ISOINDOLE-1,3(2H,3AH)-DIONE, (3A.ALPHA.,4.BETA.,4A.ALPHA.,5A.ALPHA.,6.BETA.,6A.ALPHA.)-

METABOLITE INACTIVE -> PARENT

Amount:

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Related Record

Type

Details


					F925RR824R

TECOVIRIMAT

ACTIVE MOIETY

Comments:

broad-spectrum antiviral activity against other orthopoxviruses, including VARV, CPXV, rabbitpox virus (RPXV), MPXV, ectromelia virus (ECTV), and camelpox virus (CMLV) with EC50 values in the submicromolar range. Targets the p37 protein.

Amount:

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Name	Property Type	Amount	Parameters
Tmax	PHARMACOKINETIC	[4 to 6] hours (average)	ORAL ADMINISTRATION DOSE 600 mg (average)

Biological Half-life	PHARMACOKINETIC	21 hours (average)

blood-to-plasma ratio	PHARMACOKINETIC	[0.62 to 0.9] (average)

Volume of Distribution	PHARMACOKINETIC	1030 LITERS (average)

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator