Valbenazine tosylate monohydrate

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H38N2O4.2C7H8O3S.H2O
Molecular Weight	780.988
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of Valbenazine tosylate monohydrate

Structure Search

SMILES

O.CC1=CC=C(C=C1)S(O)(=O)=O.CC2=CC=C(C=C2)S(O)(=O)=O.[H][C@]34C[C@@H](OC(=O)[C@@H](N)C(C)C)[C@H](CC(C)C)CN3CCC5=CC(OC)=C(OC)C=C45

InChI

InChIKey=BZOQQAYRXXEDQK-SPJWOFKYSA-N

InChI=1S/C24H38N2O4.2C7H8O3S.H2O/c1-14(2)9-17-13-26-8-7-16-10-21(28-5)22(29-6)11-18(16)19(26)12-20(17)30-24(27)23(25)15(3)4;2*1-6-2-4-7(5-3-6)11(8,9)10;/h10-11,14-15,17,19-20,23H,7-9,12-13,25H2,1-6H3;2*2-5H,1H3,(H,8,9,10);1H2/t17-,19-,20-,23+;;;/m1.../s1

HIDE SMILES / InChI

Molecular Formula	C24H38N2O4
Molecular Weight	418.5695
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

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	C7H8O3S
Molecular Weight	172.202
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/9094204 | http://adisinsight.springer.com/drugs/800046946

(+)-alpha-Dihydrotetrabenazine (HTBZ) is an active component of tetrabenazine. Tetrabenazine is a mixture of closely-related compounds (isomers) and is readily metabolized in the human body to HTBZ and related isomers. Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorder and is marketed under the trade names Nitoman in Canada and Xenazine in New Zealand and some parts of Europe, and is also available in the USA as an orphan drug. (+)-alpha-Dihydrotetrabenazine and related benzo[a]quinolizines have been labeled with tritium and carbon-11 radioisotopes and used for in vitro and in vivo studies of the VMAT2 in animal and human brain. Adeptio Pharmaceuticals is developing alpha-dihydrotetrabenazine (HTBZ) for the treatment of neurological disorders. It acts by inhibiting vesicular monoamine transporter 2 (VMAT2), thereby blocking the transport of dopamine into axon terminals or into storage vesicles.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Synaptic vesicular amine transporter 57 Target ID: CHEMBL4828 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9094204 \| https://www.ncbi.nlm.nih.gov/pubmed/19632829	Inhibitor 8297		0.97 nM [Ki]
Synaptic vesicular amine transporter 57 Target ID: Q05940 Gene ID: 6571.0 Gene Symbol: SLC18A2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/30160230	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Neurological disorders 10 Sources: http://adisinsight.springer.com/drugs/800046946	Primary		Phase I 428	Unknown Approved Use Unknown
tardive dyskinesia 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	Primary		Approved 8429	INGREZZA Approved Use INGREZZA is indicated for the treatment of adults with tardive dyskinesia Launch Date 2017

C_max

Value	Dose	Analyte	Population
0.19 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
39.4 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241oirg1s000clinpharmr.pdf	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
64 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
35.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
31.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
56.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
9.22 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
695 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241oirg1s000clinpharmr.pdf	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1110 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
630 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1150 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1840 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
32 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
18.5 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241oirg1s000clinpharmr.pdf	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
19 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
19 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
36% OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241oirg1s000clinpharmr.pdf	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		NBI-98782 unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	unhealthy, 18 - 85 years n = 110 Health Status: unhealthy Condition: schizophrenia or schizoaffective disorder, or mood disorder Age Group: 18 - 85 years Sex: M+F Population Size: 110 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	Disc. AE: Syncope... AEs leading to discontinuation/dose reduction: Syncope (1 patient) Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf
80 mg 1 times / day steady, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: steady Dose: 80 mg, 1 times / day Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	unhealthy, 18 - 85 years n = 112 Health Status: unhealthy Condition: schizophrenia or schizoaffective disorder, or mood disorder Age Group: 18 - 85 years Sex: M+F Population Size: 112 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	Disc. AE: Syncope, Cardiac failure... AEs leading to discontinuation/dose reduction: Syncope (1 patient) Cardiac failure (1 patient) Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf
40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1	unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1	Other AEs: Somnolence, Anticholinergic syndrome... Other AEs: Somnolence (10.9%) Anticholinergic syndrome (5.4%) Balance disorder (4.1%) Headache (3.4%) Akathisia (2.7%) Vomiting (2.6%) Nausea (2.3%) Arthralgia (2.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1
80 mg 1 times / day steady, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: steady Dose: 80 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: 8.1	unhealthy, 26 - 84 years Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: 8.1	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: 8.1

AEs

AE	Significance	Dose	Population
Syncope	1 patient Disc. AE	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	unhealthy, 18 - 85 years n = 110 Health Status: unhealthy Condition: schizophrenia or schizoaffective disorder, or mood disorder Age Group: 18 - 85 years Sex: M+F Population Size: 110 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf
Cardiac failure	1 patient Disc. AE	80 mg 1 times / day steady, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: steady Dose: 80 mg, 1 times / day Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	unhealthy, 18 - 85 years n = 112 Health Status: unhealthy Condition: schizophrenia or schizoaffective disorder, or mood disorder Age Group: 18 - 85 years Sex: M+F Population Size: 112 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf
Syncope	1 patient Disc. AE	80 mg 1 times / day steady, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: steady Dose: 80 mg, 1 times / day Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	unhealthy, 18 - 85 years n = 112 Health Status: unhealthy Condition: schizophrenia or schizoaffective disorder, or mood disorder Age Group: 18 - 85 years Sex: M+F Population Size: 112 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf
Somnolence	10.9%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1	unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1
Arthralgia	2.3%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1	unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1
Nausea	2.3%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1	unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1
Vomiting	2.6%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1	unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1
Akathisia	2.7%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1	unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1
Headache	3.4%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1	unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1
Balance disorder	4.1%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1	unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1
Anticholinergic syndrome	5.4%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1	unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf Page: Table 1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 OAT1 599 OAT3 642 OCT2 647 OATP1B1 788 OATP1B3 706 CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A4/5 278	esterase 72 UGT 192 P-gp 1537	CYP1A2 701 CYP2B6 547 CYP3A4/5 124

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Orig1s000PharmR.pdf#page=32 Page: 32.0	yes [IC50 14.2 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Orig1s000PharmR.pdf#page=25 Page: 25.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=7 Page: 7;30	yes
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Orig1s000PharmR.pdf#page=30 Page: 30.0	yes
esterase 72	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Orig1s000PharmR.pdf#page=30 Page: 30.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=22 Page: 22;30	yes	yes (co-administration study) Comment: administered with ketoconazole: (similar PK parameters with parent drug) approximately 1.5-fold and 2-fold increase in the Cmax and AUC0-inf, respectively; administered with rifampin: about 50% decrease in Cmax and 80% decrease in AUC0-inf Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=22 Page: 22;30

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Orig1s000PharmR.pdf#page=24 Page: 24.0

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA004RNP	https://www.aablocks.com/goods/Goods/detail?id=AA004RNP
Acorn PharmaTech	ACN-052011	http://www.acornpharmatech.com/
Ambinter	Amb19131894	http://www.ambinter.com/reference/19131894
ApexBio Technology	B1268	http://www.apexbt.com/nbi-98782.html
BioCrick	BCC4277	http://www.biocrick.com/NBI-98782-BCC4277.html
Boerchem	BC686671	http://www.boerchem.com/?product_40360.html
Chem Scene	CS-1899	http://www.chemscene.com/85081-18-1.html
ChemMol	30116008	http://www.chemmol.com/chemmol/30116008.html
ChemMol	44011746	http://www.chemmol.com/chemmol/44011746.html
ChemMol	49422526	http://www.chemmol.com/chemmol/49422526.html
ChemMol	99084375	http://www.chemmol.com/chemmol/99084375.html
Chemspace	CSSB00102513434	https://chem-space.com/CSSB00102513434
MedChem Express	HY-15793	https://www.medchemexpress.com/nbi-98782.html
MuseChem	I005104	https://www.musechem.com/product/I005104.html
OChem	21713	http://www.ocheminc.com/index.php?act=psearch&pid=081D181
Smolecule	S649206	https://www.smolecule.com/products/s649206
Synblock Inc	SB18190	http://www.synblock.com/product/85081-18-1.html
THE BioTek	bt-352749	https://www.thebiotek.com/product/others/bt-352749
Yuhao Chemical	YH89670	http://www.chemyuhao.com/85081-18-1.html

PubMed

Title	Date	PubMed
A ring-closing metathesis-based approach to the synthesis of (+)-tetrabenazine.	2012 Jul 20	22742980
Early synaptic dysfunction induced by α-synuclein in a rat model of Parkinson's disease.	2017 Jul 25	28743955
Differences in Dihydrotetrabenazine Isomer Concentrations Following Administration of Tetrabenazine and Valbenazine.	2017 Sep	28776237

Patents

Sample Use Guides

In Vivo Use Guide

Single dose administration of (+)-alpha-Dihydrotetrabenazine (HTBZ), escalating dosage amounts 7.5 - 30 mg orally

Route of Administration: Oral

In Vitro Use Guide

(+)-alpha-Dihydrotetrabenazine is a vesicular monoamine transporter (VMAT2) inhibtior with an Ki value of 0.97 nM. IC50 value: 0.97± 0.48 nM. The (+)-isomer showed high affinity in vitro (Ki = 0.97 +/- 0.48 nM) for the vesicular monoamine transporter (VMAT2) in rat brain striatum, whereas the (-)-isomer was inactive (Ki = 2.2 +/- 0.3 uM).

Substance Class	Chemical Created by `admin` on `Sat Dec 16 19:13:56 GMT 2023` Edited by `admin` on `Sat Dec 16 19:13:56 GMT 2023`
Record UNII	EY9Y2J33NX
Record Status	`Validated (UNII)`
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Name

Type

Language

Valbenazine tosylate monohydrate

Common Name

English

Valbenazine ditosylate hydrate

Common Name

English

L-Valine, (2R,3R,11bR)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-yl ester, 4-methylbenzenesulfonate, hydrate (1:2:1)

Systematic Name

English

Code System Code Type Description

FDA UNII

EY9Y2J33NX

Created by admin on Sat Dec 16 19:13:56 GMT 2023 , Edited by admin on Sat Dec 16 19:13:56 GMT 2023

PRIMARY

PUBCHEM

164888925

Created by admin on Sat Dec 16 19:13:56 GMT 2023 , Edited by admin on Sat Dec 16 19:13:56 GMT 2023

PRIMARY

CAS

2243207-60-3

Created by admin on Sat Dec 16 19:13:56 GMT 2023 , Edited by admin on Sat Dec 16 19:13:56 GMT 2023

PRIMARY

Related Record Type Details


					5SML1T733B

Valbenazine tosylate

ANHYDROUS->SOLVATE

Amount:

Related Record Type Details


					IFRYDMLSGE

(+)-α-Dihydrotetrabenazine

ACTIVE MOIETY

Amount:

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/9094204 | http://adisinsight.springer.com/drugs/800046946

CNS Activity

Originator

Approval Year

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Approved Use

Approved Use

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T1/2

Funbound

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Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9094204 | http://adisinsight.springer.com/drugs/800046946

C_max

T_1/2

F_unbound

Drug as perpetrator