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Details

Stereochemistry ACHIRAL
Molecular Formula C38H36N6O7.CH4O3S.H2O
Molecular Weight 802.849
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ENCEQUIDAR MESYLATE

SMILES

O.CS(O)(=O)=O.COC1=CC(NC(=O)C2=CC(=O)C3=CC=CC=C3O2)=C(C=C1OC)C4=NN(N=N4)C5=CC=C(CCN6CCC7=CC(OC)=C(OC)C=C7C6)C=C5

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 C38H36N6O7
Molecular Weight 688.7284
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula CH4O3S
Molecular Weight 96.106
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
Metabolism of a new P-glycoprotein inhibitor HM-30181 in rats using liquid chromatography/electrospray mass spectrometry.
2006
Simultaneous determination of paclitaxel and a new P-glycoprotein inhibitor HM-30181 in rat plasma by liquid chromatography with tandem mass spectrometry.
2006 Mar
Characterization of human liver cytochrome P-450 enzymes involved in the O-demethylation of a new P-glycoprotein inhibitor HM-30181.
2007 Aug
Response of brain specific microenvironment to P-glycoprotein inhibitor: an important factor determining therapeutic effect of P-glycoprotein inhibitor on brain metastatic tumors.
2008 Oct
Selective inhibition of MDR1 (ABCB1) by HM30181 increases oral bioavailability and therapeutic efficacy of paclitaxel.
2010 Feb 10
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 Dec 16 08:28:49 UTC 2023
Edited
by admin
on Sat Dec 16 08:28:49 UTC 2023
Record UNII
XRZ6538A8R
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ENCEQUIDAR MESYLATE
USAN  
Official Name English
HM-30181 METHANESULFONATE MONOHYDRATE
Code English
HM30181 METHANESULFONATE MONOHYDRATE
Code English
ENCEQUIDAR MESYLATE [USAN]
Common Name English
ORAXOL COMPONENT HM-30181A
Common Name English
HM-30181A
Code English
ENCEQUIDAR MESYLATE MONOHYDRATE
Common Name English
HM30181A
Code English
HM-30181 MESYLATE 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 Dec 16 08:28:49 UTC 2023 , Edited by admin on Sat Dec 16 08:28:49 UTC 2023
PRIMARY
NCI_THESAURUS
C188262
Created by admin on Sat Dec 16 08:28:49 UTC 2023 , Edited by admin on Sat Dec 16 08:28:49 UTC 2023
PRIMARY
PUBCHEM
131801109
Created by admin on Sat Dec 16 08:28:49 UTC 2023 , Edited by admin on Sat Dec 16 08:28:49 UTC 2023
PRIMARY
SMS_ID
300000038705
Created by admin on Sat Dec 16 08:28:49 UTC 2023 , Edited by admin on Sat Dec 16 08:28:49 UTC 2023
PRIMARY
FDA UNII
XRZ6538A8R
Created by admin on Sat Dec 16 08:28:49 UTC 2023 , Edited by admin on Sat Dec 16 08:28:49 UTC 2023
PRIMARY
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ANHYDROUS->SOLVATE
PARENT -> SALT/SOLVATE
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ACTIVE MOIETY