REMIMAZOLAM BESYLATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H19BrN4O2.C6H6O3S
Molecular Weight	597.48
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(=O)(=O)C1=CC=CC=C1.COC(=O)CC[C@@H]2N=C(C3=NC=CC=C3)C4=CC(Br)=CC=C4N5C(C)=CN=C25

InChI

InChIKey=QMTKNJZIWGTNTE-LMOVPXPDSA-N

InChI=1S/C21H19BrN4O2.C6H6O3S/c1-13-12-24-21-17(7-9-19(27)28-2)25-20(16-5-3-4-10-23-16)15-11-14(22)6-8-18(15)26(13)21;7-10(8,9)6-4-2-1-3-5-6/h3-6,8,10-12,17H,7,9H2,1-2H3;1-5H,(H,7,8,9)/t17-;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27496519 | https://clinicaltrials.gov/ct2/show/NCT02296892 | https://www.ncbi.nlm.nih.gov/pubmed/29723512 | https://www.paion.com/pipeline/portfolio/remimazolam/

Remimazolam is an intravenous benzodiazepine sedative-hypnotic with rapid onset and offset of action. This compound undergoes organ-independent metabolism to an inactive metabolite. Like other benzodiazepines, remimazolam can be reversed with flumazenil to rapidly terminate sedation and anesthesia. Phase I and II clinical trials have shown that remimazolam is safe and effective when used for procedural sedation. Phase III clinical trials have been completed investigating efficacy and safety in patients undergoing bronchoscopy and colonoscopy. The developer of this drug has suggested that intensive care unit sedation (beyond 24 hours) could be another possible indication for further development, since it is unlikely that prolonged infusions or higher doses of remimazolam would result in accumulation and extended effect.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; benzodiazepine site 38 Target ID: CHEMBL2109243 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21154153 \| https://medcraveonline.com/JACCOA/JACCOA-04-00166.pdf	Agonist 2678

C_max

Value	Dose	Analyte	Population
1882 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22190555/	0.1 mg/kg single, intravenous dose: 0.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	REMIMAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6095 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22190555/	0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	REMIMAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
189.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22190555/	0.01 mg/kg single, intravenous dose: 0.01 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	REMIMAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
105.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22190555/	0.1 mg/kg single, intravenous dose: 0.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	REMIMAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
339.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22190555/	0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	REMIMAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
11.49 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22190555/	0.01 mg/kg single, intravenous dose: 0.01 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	REMIMAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
0.794 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22190555/	0.1 mg/kg single, intravenous dose: 0.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	REMIMAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.72 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22190555/	0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	REMIMAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.597 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22190555/	0.01 mg/kg single, intravenous dose: 0.01 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	REMIMAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
10 mg 1 times / day multiple, intravenous (median) Recommended Dose: 10 mg, 1 times / day Route: intravenous Route: multiple Dose: 10 mg, 1 times / day Co-administed with:: fentanyl(50 to 75 ug intravenous; 25 ug every 5 to 10 minutes were allowed until analgesia was adequate) Sources: https://pubmed.ncbi.nlm.nih.gov/29723512/	unhealthy, adults n = 296 Health Status: unhealthy Condition: colonoscopy Age Group: adults Sex: M+F Population Size: 296 Sources: https://pubmed.ncbi.nlm.nih.gov/29723512/	Other AEs: Bradypnea, Hypoxia... Other AEs: Bradypnea (1.4%) Hypoxia (1%) Respiratory depression (0.3%) Nausea (1.7%) Vomiting (1%) Headache (1.7%) Dizziness (1%) Presyncope (0.7%) Hematocrit decreased (0.3%) Infections and infestations (0.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/29723512/
10 mg 1 times / day multiple, intravenous (median) Recommended Dose: 10 mg, 1 times / day Route: intravenous Route: multiple Dose: 10 mg, 1 times / day Co-administed with:: fentanyl(50 to 75 ug intravenous; 25 ug every 5 to 10 minutes were allowed until analgesia was adequate) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212295s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/29723512/	unhealthy, adults n = 296 Health Status: unhealthy Condition: colonoscopy Age Group: adults Sex: M+F Population Size: 296 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212295s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/29723512/	Other AEs: Hypotension, Hypertension... Other AEs: Hypotension (39%) Hypertension (20%) Bradycardia (11%) Diastolic hypertension (10%) Tachycardia (8%) Diastolic hypotension (8%) Systolic hypertension (5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212295s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/29723512/
10 mg 1 times / day multiple, intravenous (median) Recommended Dose: 10 mg, 1 times / day Route: intravenous Route: multiple Dose: 10 mg, 1 times / day Co-administed with:: fentanyl(50 to 75 ug intravenous; 25 ug every 5 to 10 minutes were allowed until analgesia was adequate) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212295s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/30292760/	unhealthy, adults n = 303 Health Status: unhealthy Condition: Bronchoscopy Age Group: adults Sex: M+F Population Size: 303 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212295s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/30292760/	Disc. AE: Bradycardia, Hypertension... Other AEs: Hypotension, Hypertension... AEs leading to discontinuation/dose reduction: Bradycardia (0.33%) Hypertension (0.33%) Hypotension (0.33%) Hypoxia (0.33%) Respiratory rate increased (0.33%) Other AEs: Hypotension (grade 1, 33%) Hypertension (grade 1, 28%) Diastolic hypertension (grade 1, 25%) Systolic hypertension (grade 1, 22%) Hypoxia (grade 1, 22%) Respiratory rate increased (grade 1, 14%) Diastolic hypotension (grade 1, 14%) Nausea (grade 1, 4%) Bradycardia (grade 1, 4%) Pyrexia (grade 1, 4%) Headache (grade 1, 3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212295s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/30292760/
10 mg 1 times / day multiple, intravenous (median) Recommended Dose: 10 mg, 1 times / day Route: intravenous Route: multiple Dose: 10 mg, 1 times / day Co-administed with:: fentanyl(50 ug intravenous; 25 ug every 5 to 10 minutes were allowed until analgesia was adequate) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212295s000lbl.pdf	unhealthy, adults n = 31 Health Status: unhealthy Condition: Bronchoscopy Age Group: adults Sex: M+F Population Size: 31 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212295s000lbl.pdf	Other AEs: Hypotension, Hypertension... Other AEs: Hypotension (58%) Hypertension (42%) Respiratory acidosis (19%) Diastolic hypertension (10%) Systolic hypertension (6%) Bradycardia (3%) Respiratory rate decreased (3%) Diastolic hypotension (3%) Blood pressure diastolic increased (3%) Blood pressure increased (3%) Blood pressure systolic increased (3%) Upper respiratory tract infection (3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212295s000lbl.pdf
33.16 mg single, intravenous Highest studied dose Dose: 33.16 mg Route: intravenous Route: single Dose: 33.16 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf	unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf
19.058 mg single, intravenous (mid range) Studied dose Dose: 19.058 mg Route: intravenous Route: single Dose: 19.058 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf	unhealthy n = 165 Health Status: unhealthy Population Size: 165 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf	Other AEs: Hypoxia, Bradycardia... Other AEs: Hypoxia (15.8%) Bradycardia (9.7%) Hypotension (53.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf
20 mg single, intravenous Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf	Other AEs: QT interval prolonged... Other AEs: QT interval prolonged Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf
28.43 mg single, intravenous (mid range) Studied dose Dose: 28.43 mg Route: intravenous Route: single Dose: 28.43 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf	unhealthy n = 6 Health Status: unhealthy Population Size: 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf	Other AEs: Hypoxia, Hypotension... Other AEs: Hypoxia (33%) Hypotension (50%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf
9.686 mg single, intravenous (mid range) Studied dose Dose: 9.686 mg Route: intravenous Route: single Dose: 9.686 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf	unhealthy n = 459 Health Status: unhealthy Population Size: 459 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf	Other AEs: Hypoxia, Bradycardia... Other AEs: Hypoxia (14.6%) Bradycardia (7%) Hypotension (40.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf
0.2 mg/kg single, intravenous Studied dose Dose: 0.2 mg/kg Route: intravenous Route: single Dose: 0.2 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf	unhealthy n = 25 Health Status: unhealthy Condition: upper endoscopy Population Size: 25 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf	Other AEs: Hypoxia... Other AEs: Hypoxia (24%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000MedR.pdf

AEs

Overview

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

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP1A2 1524 OAT3 642 OCT2 647 OATP1B1 788 OATP1B3 706 OAT1 599 BCRP 699 P-gp 1461 BSEP 402 MATE1 306 MATE2 263 MRP2 383 MRP3 157 MRP4 204	CYP1A2 1054 OATP1B1 406 OATP1B3 350 BCRP 561 P-gp 1537 UGT 192	CYP1A2 701

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 29.2 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 578 uM]	CNS7054 3
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 >100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 >100 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 >100 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 >100 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 >100 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 >600 uM]	CNS7054 3
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 >600 uM]	CNS7054 3
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 >600 uM]	CNS7054 3
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 >600 uM]	CNS7054 3
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 >600 uM]	CNS7054 3
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 >600 uM]	CNS7054 3
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no	CNS7054 3
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no	CNS7054 3
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no	CNS7054 3
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no	CNS7054 3
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no	CNS7054 3
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no	CNS7054 3
MRP3 207	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no
MRP3 207	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no	CNS7054 3
MRP4 238	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no
MRP4 238	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no	CNS7054 3
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no	CNS7054 3
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no	CNS7054 3
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no	CNS7054 3
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	weak [IC50 10 uM]		unlikely Comment: Cmax<1mkM Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	weak [IC50 100 uM]		unlikely Comment: Cmax<1mkM Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	weak [IC50 100 uM]		unlikely Comment: Cmax<1mkM Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	weak [IC50 >100 uM]		unlikely Comment: Cmax<1mkM Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	yes [IC50 500 uM]	CNS7054 3	unlikely Comment: Cmax<4mkM Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	yes [IC50 500 uM]	CNS7054 3	unlikely Comment: Cmax<4mkM Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	yes [IC50 >50 uM]	CNS7054 3	unlikely Comment: Cmax<4mkM Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	yes [Inhibition 100 uM]
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	yes [Inhibition 100 uM]
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	yes [Inhibition 100 uM]

Drug as victim

Target	Modality	Activity	Metabolite
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	likely	CNS7054 3
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	likely	CNS7054 3
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	no [IC50 63.3 uM]
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no	CNS7054 3
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	no	CNS7054 3
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	yes	CNS7054 3

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000PharmR.pdf#page=58 Page: 58.0
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212295Orig1s000PharmR.pdf#page=58 Page: 58.0		CNS7054 3

Sourcing

Vendor/Aggregator	ID	URL
Achemtek	0102-013440	http://www.achemtek.com/308242-62-8
Acorn PharmaTech	ACN-029380	http://www.acornpharmatech.com/
Ambinter	Amb24053933	http://www.ambinter.com/reference/24053933
Aurora Fine Chemicals LLC	A24.140.976	http://online.aurorafinechemicals.com/info?ID=A24.140.976
AvaChem Scientific	4523B	http://www.avachem.com/productSearch.asp?4523B
Boerchem	BC600571	http://www.boerchem.com/?product_43406.html
Chem Scene	CS-0003605	http://www.chemscene.com/308242-62-8.html
ChemFish Tokyo co.,ltd	9867812	http://www.chemfish.co.jp/index.php?id=3934&project=product
Chemspace	CSSB00032005504	https://chem-space.com/CSSB00032005504
DC Chemicals	DC7009	http://www.dcchemicals.com/product_show-CNS_7056.html
Hairui	RESA034	http://www.hairuichem.com/en/product/308242-62-8.html
Lab Network	LN01310290	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01310290
MedChem Express	HY-14867	https://www.medchemexpress.com/remimazolam.html
MuseChem	I009004	https://www.musechem.com/product/I009004.html
Smolecule	S541196	http://www.smolecule.com/products/s541196
Synblock Inc	SB17134	http://www.synblock.com/product/308242-62-8.html
THE BioTek	bt-280042	https://www.thebiotek.com/product/inhibitors/bt-280042
THE BioTek	bt-340262	https://www.thebiotek.com/product/others/bt-340262

Name

Type

Language

REMIMAZOLAM BESYLATE

Official Name

English

METHYL 3-((4S)-8-BROMO-1-METHYL-6-(PYRIDIN-2-YL)-4H-IMIDAZO(1,2-A)(1,4)BENZODIAZEPIN-4-YL)PROPANOATE, MONOBENZENESULFONATE

Systematic Name

English

ONO-IN-251

Code

English

BIPRAZINE PF

Common Name

English

CNS-7056B

Code

English

GW-502056X

Code

English

REMIMAZOLAM BESYLATE [ORANGE BOOK]

Common Name

English

GW502056X

Code

English

REMIMAZOLAM BESILATE

Official Name

English

SP148.5

Code

English

REMIMAZOLAM BESYLATE [MI]

Common Name

English

RF10007

Code

English

REMIMAZOLAM BESILATE [JAN]

Common Name

English

CNS-7056 BESYLATE

Code

English

4H-IMIDAZO(1,2-A)(1,4)BENZODIAZEPINE-4-PROPANOIC ACID, 8-BROMO-1-METHYL-6-(2-PYRIDINYL)-, (4S)-, METHYL ESTER, BENZENESULFONATE (1:1)

Systematic Name

English

ONO-2745BS

Code

English

Remimazolam besylate [WHO-DD]

Common Name

English

BYFAVO

Brand Name

English

REMIMAZOLAM BESYLATE [USAN]

Common Name

English

RF-10007

Code

English

Code System Code Type Description

CAS

1001415-66-2