LUMATEPERONE TOSYLATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H28FN3O.C7H8O3S
Molecular Weight	565.699
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC=C(C=C1)S(O)(=O)=O.[H][C@]23CCN(CCCC(=O)C4=CC=C(F)C=C4)C[C@@]2([H])C5=CC=CC6=C5N3CCN6C

InChI

InChIKey=LHAPOGAFBLSJJQ-GUTACTQSSA-N

InChI=1S/C24H28FN3O.C7H8O3S/c1-26-14-15-28-21-11-13-27(16-20(21)19-4-2-5-22(26)24(19)28)12-3-6-23(29)17-7-9-18(25)10-8-17;1-6-2-4-7(5-3-6)11(8,9)10/h2,4-5,7-10,20-21H,3,6,11-16H2,1H3;2-5H,1H3,(H,8,9,10)/t20-,21-;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/30859959 | https://www.ncbi.nlm.nih.gov/pubmed/30449883 | https://www.drugbank.ca/drugs/DB06077

Lumateperone (ITI-722/ITI-007) is a dual 5HT2A receptor antagonist/dopamine phosphoprotein modulator (DPPM) for the treatment of schizophrenia. It is an orally available compound which combines potent 5HT2A receptor antagonism with cell-type-specific modulation of phosphoprotein pathways downstream of dopamine receptors. Lumateperone was developed by Intra-Cellular Therapies, Inc., and is being evaluated for the treatment of schizophrenia and bipolar depression. In 3 efficacy studies in patients with acute schizophrenia, lumateperone was well-tolerated with a favorable safety profile, and in 2 studies of 3 demonstrated significantly superior efficacy over placebo.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serotonin 2a (5-HT2a) receptor 231 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24559051	Antagonist 2778	0.54 nM [Ki]
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24559051	Antagonist 2778	32.0 nM [Ki]
Serotonin transporter 178 Target ID: CHEMBL228 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24559051	Inhibitor 8297	61.0 nM [Ki]

C_max

Value	Dose	Co-administered	Analyte	Population
19.7 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf	42 mg 1 times / day steady-state, oral dose: 42 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LUMATEPERONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
64.2 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf	42 mg 1 times / day steady-state, oral dose: 42 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LUMATEPERONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.1 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf	42 mg 1 times / day steady-state, oral dose: 42 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LUMATEPERONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
4.4% OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf	42 mg 1 times / day steady-state, oral dose: 42 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LUMATEPERONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
42 mg 1 times / day steady, oral Recommended Dose: 42 mg, 1 times / day Route: oral Route: steady Dose: 42 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209500s000lbl.pdf	unhealthy, 19 to 60 years n = 406 Health Status: unhealthy Condition: Schizophrenia Age Group: 19 to 60 years Sex: M+F Population Size: 406 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209500s000lbl.pdf	Other AEs: Somnolence, Nausea... Other AEs: Somnolence (24%) Nausea (9%) Dry mouth (6%) Dizziness (5%) Creatine phosphokinase increased (4%) Fatigue (3%) Vomiting (3%) Transaminases increased (2%) Decreased appetite (2%) Spasm of muscle Swallowing difficult Difficulty breathing Protrusion tongue Extrapyramidal symptoms (6.7%) Akathisia Extrapyramidal disorder Muscle spasms Restlessness Musculoskeletal stiffness Dyskinesia Dystonia Muscle twitching Tardive dyskinesia Tremor Drooling Muscle contractions involuntary Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209500s000lbl.pdf
60 mg 1 times / day steady, oral Studied dose Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30449883/	unhealthy, 26 to 57 years n = 10 Health Status: unhealthy Condition: Schizophrenia Age Group: 26 to 57 years Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/30449883/	Other AEs: Headache, Sedation... Other AEs: Headache (grade 1-2, 40%) Sedation (grade 1, 40%) Sources: https://pubmed.ncbi.nlm.nih.gov/30449883/
60 mg 1 times / day steady, oral Studied dose Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26444072/	unhealthy, mean 38.3 years n = 84 Health Status: unhealthy Condition: Schizophrenia Age Group: mean 38.3 years Sex: M+F Population Size: 84 Sources: https://pubmed.ncbi.nlm.nih.gov/26444072/	Other AEs: Somnolence, Dry mouth... Other AEs: Somnolence (16.7%) Dry mouth (4.8%) Nausea (6%) Dizziness (4.8%) Akathisia (1.2%) Tachycardia (1.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/26444072/
90 mg 1 times / day steady, oral (mean) Studied dose Dose: 90 mg, 1 times / day Route: oral Route: steady Dose: 90 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26444072/	unhealthy, mean 39.7 years n = 167 Health Status: unhealthy Condition: Schizophrenia Age Group: mean 39.7 years Sex: M+F Population Size: 167 Sources: https://pubmed.ncbi.nlm.nih.gov/26444072/	Disc. AE: Dry mouth, Schizophrenia aggravated... AEs leading to discontinuation/dose reduction: Dry mouth (0.6%) Schizophrenia aggravated (0.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/26444072/
120 mg 1 times / day steady, oral Highest studied dose Dose: 120 mg, 1 times / day Route: oral Route: steady Dose: 120 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26444072/	unhealthy, mean 41.1 years n = 83 Health Status: unhealthy Condition: Schizophrenia Age Group: mean 41.1 years Sex: M+F Population Size: 83 Sources: https://pubmed.ncbi.nlm.nih.gov/26444072/	Other AEs: Somnolence, Dry mouth... Other AEs: Somnolence (32.5%) Dry mouth (8.4%) Nausea (4.8%) Dizziness (8.4%) Akathisia (2.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/26444072/
42 mg 1 times / day multiple, oral Recommended Dose: 42 mg, 1 times / day Route: oral Route: multiple Dose: 42 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31913424/	unhealthy, mean 42.4 years n = 150 Health Status: unhealthy Condition: Schizophrenia Age Group: mean 42.4 years Sex: M+F Population Size: 150 Sources: https://pubmed.ncbi.nlm.nih.gov/31913424/	Disc. AE: Headache, Orthostatic hypotension... Other AEs: Headache, Somnolence... AEs leading to discontinuation/dose reduction: Headache (1.3%) Orthostatic hypotension (grade 3, 0.7%) Other AEs: Headache (grade 1-2, 19.3%) Somnolence (grade 1-2, 17.3%) Sedation (grade 1-2, 12.7%) Nausea (grade 1-2, 10.7%) Dry mouth (grade 1-2, 7.3%) Dizziness (grade 1-2, 6.7%) Constipation (grade 1-2, 6.7%) Fatigue (grade 1-2, 5.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/31913424/
28 mg 1 times / day multiple, oral Studied dose Dose: 28 mg, 1 times / day Route: oral Route: multiple Dose: 28 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31913424/	unhealthy, mean 43.5 years n = 150 Health Status: unhealthy Condition: Schizophrenia Age Group: mean 43.5 years Sex: M+F Population Size: 150 Sources: https://pubmed.ncbi.nlm.nih.gov/31913424/	Disc. AE: Convulsions... Other AEs: Akathisia, Headache... AEs leading to discontinuation/dose reduction: Convulsions (grade 3, 0.7%) Other AEs: Akathisia (grade 1-2, 4%) Headache (grade 1-2, 16%) Somnolence (grade 1-2, 11.3%) Sedation (grade 1-2, 9.3%) Nausea (grade 1-2, 4.7%) Dry mouth (grade 1-2, 6%) Dizziness (grade 1-2, 4.7%) Constipation (grade 1-2, 4%) Fatigue (grade 1-2, 4.7%) Akathisia (grade 1-2, 1.3%) Dyskinesia (grade 1-2, 1.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/31913424/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 OATP1B1 788 OAT1 599 OAT3 642 OCT2 647	UGT1A1 418 UGT1A4 347 UGT2B15 203 AKR1C1 19 AKR1B10 2 AKR1C4 6 CYP2C8 693 CYP1A2 1054 P-gp 1537 BCRP 561	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Metabolite
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	no	IC200131 2
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	no	IC200131 2
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	no	IC200131 2
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	no	IC200131 2
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=130 Page: 130.0	yes
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	yes
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=130 Page: 130.0	yes
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	yes
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	yes
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	yes
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=130 Page: 130.0	yes
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=64 Page: 64.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=130 Page: 130.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=130 Page: 130.0	no
AKR1B10 2	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=127 Page: 127.0	yes
AKR1C1 19	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=127 Page: 127.0	yes
AKR1C4 6	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=127 Page: 127.0	yes
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=127 Page: 127.0	yes
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=127 Page: 127.0	yes
UGT1A1 418	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=127 Page: 127.0	yes
UGT1A4 347	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=127 Page: 127.0	yes
UGT2B15 203	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=127 Page: 127.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=127 Page: 127.0	yes	yes (co-administration study) Comment: Coadministration of lumateperone 14 mg with itraconazole 200 mg (strong CYP3A4 inhibitor) increased lumateperone exposure approximately 4-fold in patients with schizophrenia. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000MultidisciplineR.pdf#page=127 Page: 127.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209500Orig1s000OtherR.pdf#page=94 Page: 94.0

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00I5U2	https://www.aablocks.com/goods/Goods/detail?id=AA00I5U2
Ambinter	Amb24183497	http://www.ambinter.com/reference/24183497
Angel Pharmatech	AG-15617	http://www.angelpharmatech.com/313368-91-1.html
Angene	AGN-PC-0WAMBU	http://www.angenechemical.com/productshow/AGN-PC-0WAMBU.html
Ark Pharm	AK173827	http://www.arkpharminc.com/products/313368-91-1.html
BOC Sciences	313368-91-1	https://www.bocsci.com/product/lumateperone-cas-313368-91-1-470913.html
BioChemPartner	BCP24038	http://www.biochempartner.com/313368-91-1-BCP24038
Chemspace	CSSB00016994610	https://chem-space.com/CSSB00016994610
DC Chemicals	DC22906	http://www.dcchemicals.com/product_show-DC22906.html
Excenen	EX-A3605	https://www.excenen.com/searchresultlist.php?id=EX-A3605
Hairui	LUJB004	http://www.hairuichem.com/en/product/313368-91-1.html
Lab Network	LN03247748	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN03247748
Smolecule	S531028	http://www.smolecule.com/products/s531028
Synblock Inc	SB17147	http://www.synblock.com/product/313368-91-1.html
THE BioTek	bt-270151	https://www.thebiotek.com/product/inhibitors/bt-270151
abcr GmbH	AB464020	http://www.abcr.de/shop/en/AB464020
eNovation Chemicals	D572903	http://www.enovationchem.com/productDetails.asp?productID=D572903

PubMed

Title	Date	PubMed

Patents

Name

Type

Language

LUMATEPERONE TOSYLATE

Official Name

English

LUMATEPERONE TOSYLATE [ORANGE BOOK]

Common Name

English

1-BUTANONE, 1-(4-FLUOROPHENYL)-4-((6BR,10AS)-2,3,6B,9,10,10A-HEXAHYDRO-3-METHYL-1H-PYRIDO(3',4':4,5)PYRROLO(1,2,3-DE)QUINOXALIN-8(7H)-YL)-, 4-METHYLBENZENESULFONATE (1:1)

Systematic Name

English

1-(4-FLUOROPHENYL)-4-((6BR,10AS)-3-METHYL-2,3,6B,9,10,10A-HEXAHYDRO-1H-PYRIDO(3',4':4,5)PYRROLO(1,2,3-DE)QUINOXALIN-8(7H)-YL)BUTAN-1-ONE 4-METHYLBENZENESULFONATE (1:1)

Systematic Name

English

CAPLYTA

Brand Name

English

Lumateperone tosylate [WHO-DD]

Common Name

English

ITI-007 TOSYLATE

Code

English

LUMATEPERONE TOSYLATE [USAN]

Common Name

English

Code System Code Type Description

RXCUI

2275731