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Details

Stereochemistry ACHIRAL
Molecular Formula C38H36N6O7.CH4O3S.H2O
Molecular Weight 802.852
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ENCEQUIDAR MESYLATE MONOHYDRATE

SMILES

COc1cc2CCN(CCc3ccc(cc3)-n4nc(-c5cc(c(cc5NC(=O)c6cc(=O)c7ccccc7o6)OC)OC)nn4)Cc2cc1OC.CS(=O)(=O)O.O

InChI

InChIKey=DGJLRUWQERZYGC-UHFFFAOYSA-N
InChI=1S/C38H36N6O7.CH4O3S.H2O/c1-47-32-17-24-14-16-43(22-25(24)18-33(32)48-2)15-13-23-9-11-26(12-10-23)44-41-37(40-42-44)28-19-34(49-3)35(50-4)20-29(28)39-38(46)36-21-30(45)27-7-5-6-8-31(27)51-36;1-5(2,3)4;/h5-12,17-21H,13-16,22H2,1-4H3,(H,39,46);1H3,(H,2,3,4);1H2

HIDE SMILES / InChI

Molecular Formula CH4O3S
Molecular Weight 96.1068
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C38H36N6O7
Molecular Weight 688.7299
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

HM-30181 is a highly selective and potent inhibitor of Multi-drug resistance 1 (MDR1, ABCB1), also known as P-glycoprotein (P-gp). Co-administration of HM30181 greatly increased oral bioavailability of tubulin-stabilizing chemotherapeutic agent paclitaxel. Oraxol is an oral dosage form of paclitaxel administered orally with the HM30181A molecule. Oraxol offers patients with paclitaxel-responsive tumors the possibility of oral therapy without the requirement for premedication to prevent infusion-related hypersensitivity-type reactions. Current clinical data suggests the promising potential of a better clinical response and tolerability profile, which can likely to be attributed to the better pharmacokinetic profile achieved. Oraxol is presently in a Phase 3 trial in metastatic breast cancer and poised to enter into a combination study for treatment of advanced gastric cancer with ramucirumab through a clinical trial collaboration with Eli Lilly and Company.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.63 nM [IC50]
Conditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
13.4 μg/L
180 mg 1 times / day multiple, oral
dose: 180 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
22.5 μg/L
360 mg 1 times / day multiple, oral
dose: 360 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
16.2 μg/L
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
6.6 μg/L
900 mg single, oral
dose: 900 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
5.2 μg/L
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
4 μg/L
360 mg single, oral
dose: 360 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
233.1 μg × h/L
180 mg 1 times / day multiple, oral
dose: 180 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
233.1 μg × h/L
360 mg 1 times / day multiple, oral
dose: 360 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
262.3 μg × h/L
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1112.8 μg × h/L
900 mg single, oral
dose: 900 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
556.8 μg × h/L
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
697 μg × h/L
360 mg single, oral
dose: 360 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
215.2 h
180 mg 1 times / day multiple, oral
dose: 180 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
198 h
360 mg 1 times / day multiple, oral
dose: 360 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
153.5 h
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
122.8 h
900 mg single, oral
dose: 900 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
75.7 h
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
169.3 h
360 mg single, oral
dose: 360 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HM-30181 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
360 mg 1 times / day multiple, oral
Highest studied dose
Dose: 360 mg, 1 times / day
Route: oral
Route: multiple
Dose: 360 mg, 1 times / day
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: FASTED
Population Size: 8
Sources:
Other AEs: Loose stools, Epigastric discomfort...
Other AEs:
Loose stools (12.5%)
Epigastric discomfort (12.5%)
Anorexia (12.5%)
Diarrhea (50%)
Fatigue (12.5%)
Abdominal pain (50%)
Dizziness (12.5%)
Sources:
900 mg single, oral (unknown)
Highest studied dose
Dose: 900 mg
Route: oral
Route: single
Dose: 900 mg
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: FASTED
Population Size: 8
Sources:
Other AEs: Dizziness...
Other AEs:
Dizziness (12.5%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Anorexia 12.5%
360 mg 1 times / day multiple, oral
Highest studied dose
Dose: 360 mg, 1 times / day
Route: oral
Route: multiple
Dose: 360 mg, 1 times / day
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: FASTED
Population Size: 8
Sources:
Dizziness 12.5%
360 mg 1 times / day multiple, oral
Highest studied dose
Dose: 360 mg, 1 times / day
Route: oral
Route: multiple
Dose: 360 mg, 1 times / day
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: FASTED
Population Size: 8
Sources:
Epigastric discomfort 12.5%
360 mg 1 times / day multiple, oral
Highest studied dose
Dose: 360 mg, 1 times / day
Route: oral
Route: multiple
Dose: 360 mg, 1 times / day
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: FASTED
Population Size: 8
Sources:
Fatigue 12.5%
360 mg 1 times / day multiple, oral
Highest studied dose
Dose: 360 mg, 1 times / day
Route: oral
Route: multiple
Dose: 360 mg, 1 times / day
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: FASTED
Population Size: 8
Sources:
Loose stools 12.5%
360 mg 1 times / day multiple, oral
Highest studied dose
Dose: 360 mg, 1 times / day
Route: oral
Route: multiple
Dose: 360 mg, 1 times / day
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: FASTED
Population Size: 8
Sources:
Abdominal pain 50%
360 mg 1 times / day multiple, oral
Highest studied dose
Dose: 360 mg, 1 times / day
Route: oral
Route: multiple
Dose: 360 mg, 1 times / day
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: FASTED
Population Size: 8
Sources:
Diarrhea 50%
360 mg 1 times / day multiple, oral
Highest studied dose
Dose: 360 mg, 1 times / day
Route: oral
Route: multiple
Dose: 360 mg, 1 times / day
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: FASTED
Population Size: 8
Sources:
Dizziness 12.5%
900 mg single, oral (unknown)
Highest studied dose
Dose: 900 mg
Route: oral
Route: single
Dose: 900 mg
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: FASTED
Population Size: 8
Sources:
PubMed

PubMed

TitleDatePubMed
Characterization of human liver cytochrome P-450 enzymes involved in the O-demethylation of a new P-glycoprotein inhibitor HM-30181.
2007 Aug
Patents

Sample Use Guides

HM30181 was well tolerated after oral administration within the dose range evaluated (180-, 360-, 600-, and 900-mg single-dose groups and 60-, 180-, and 360-mg multiple-dose groups), with the exception of the repeated administration of 360 mg, for which gastrointestinal disorders were frequently reported. Oraxol (paclitaxel - supplied as 30-mg capsules HM30181 methansulfonate monohydrate - supplied as 15-mg HM30181AK-US) is studying in a Phase 3 trial for the treatment of breast cancer, however, treatment regimen is unknown.
Route of Administration: Oral
HM-30181 effectively blocked transepithelial transport of paclitaxel in MDCK monolayers (IC(50)=35.4nM)
Substance Class Chemical
Created
by admin
on Sat Jun 26 14:20:19 UTC 2021
Edited
by admin
on Sat Jun 26 14:20:19 UTC 2021
Record UNII
XRZ6538A8R
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ENCEQUIDAR MESYLATE MONOHYDRATE
Common Name English
HM-30181 METHANESULFONATE MONOHYDRATE
Code English
4H-1-BENZOPYRAN-2-CARBOXAMIDE, N-(2-(2-(4-(2-(3,4-DIHYDRO-6,7-DIMETHOXY-2(1H)-ISOQUINOLINYL)ETHYL)PHENYL)-2H-TETRAZOL-5-YL)-4,5-DIMETHOXYPHENYL)-4-OXO-, METHANESULFONATE, HYDRATE (1:1:1)
Systematic Name English
Code System Code Type Description
CAS
2097125-58-9
Created by admin on Sat Jun 26 14:20:19 UTC 2021 , Edited by admin on Sat Jun 26 14:20:19 UTC 2021
PRIMARY
PUBCHEM
131801109
Created by admin on Sat Jun 26 14:20:19 UTC 2021 , Edited by admin on Sat Jun 26 14:20:19 UTC 2021
PRIMARY
FDA UNII
XRZ6538A8R
Created by admin on Sat Jun 26 14:20:19 UTC 2021 , Edited by admin on Sat Jun 26 14:20:19 UTC 2021
PRIMARY
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