ENCEQUIDAR HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C38H36N6O7.ClH
Molecular Weight	725.189
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.COC1=CC2=C(CN(CCC3=CC=C(C=C3)N4N=NC(=N4)C5=CC(OC)=C(OC)C=C5NC(=O)C6=CC(=O)C7=C(O6)C=CC=C7)CC2)C=C1OC

InChI

InChIKey=KAQQJKZDBBMBEZ-UHFFFAOYSA-N

InChI=1S/C38H36N6O7.ClH/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;/h5-12,17-21H,13-16,22H2,1-4H3,(H,39,46);1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C38H36N6O7
Molecular Weight	688.7284
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/19903471 | http://www.athenex.com/oncology-innovation/oral-absorption-platform/oraxol-an-oral-formulation-of-paclitaxel/

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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
P-glycoprotein 1 52 Target ID: CHEMBL4302 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19903471	Inhibitor 8146		0.63 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 426 Sources: http://www.athenex.com/oncology-innovation/oral-absorption-platform/oraxol-an-oral-formulation-of-paclitaxel/	Primary		Phase III 651	Unknown Approved Use Unknown
Gastric cancer 54 Sources: http://www.athenex.com/oncology-innovation/oral-absorption-platform/oraxol-an-oral-formulation-of-paclitaxel/	Primary		Phase II 1133	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
13.4 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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

Value	Dose	Analyte	Population
233.1 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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

T_1/2

Value	Dose	Analyte	Population
215.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22284902/	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/22284902/	healthy n = 8 Health Status: healthy Sex: M Food Status: FASTED Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/	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: https://pubmed.ncbi.nlm.nih.gov/22284902/
900 mg single, oral (unknown) Highest studied dose Dose: 900 mg Route: oral Route: single Dose: 900 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/	healthy n = 8 Health Status: healthy Sex: M Food Status: FASTED Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/	Other AEs: Dizziness... Other AEs: Dizziness (12.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/22284902/	healthy n = 8 Health Status: healthy Sex: M Food Status: FASTED Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/
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: https://pubmed.ncbi.nlm.nih.gov/22284902/	healthy n = 8 Health Status: healthy Sex: M Food Status: FASTED Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/
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: https://pubmed.ncbi.nlm.nih.gov/22284902/	healthy n = 8 Health Status: healthy Sex: M Food Status: FASTED Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/
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: https://pubmed.ncbi.nlm.nih.gov/22284902/	healthy n = 8 Health Status: healthy Sex: M Food Status: FASTED Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/
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: https://pubmed.ncbi.nlm.nih.gov/22284902/	healthy n = 8 Health Status: healthy Sex: M Food Status: FASTED Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/
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: https://pubmed.ncbi.nlm.nih.gov/22284902/	healthy n = 8 Health Status: healthy Sex: M Food Status: FASTED Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/
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: https://pubmed.ncbi.nlm.nih.gov/22284902/	healthy n = 8 Health Status: healthy Sex: M Food Status: FASTED Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/
Dizziness	12.5%	900 mg single, oral (unknown) Highest studied dose Dose: 900 mg Route: oral Route: single Dose: 900 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/	healthy n = 8 Health Status: healthy Sex: M Food Status: FASTED Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22284902/

PubMed

Title	Date	PubMed
Metabolism of a new P-glycoprotein inhibitor HM-30181 in rats using liquid chromatography/electrospray mass spectrometry.	2006	16586459
Simultaneous determination of paclitaxel and a new P-glycoprotein inhibitor HM-30181 in rat plasma by liquid chromatography with tandem mass spectrometry.	2006 Mar	16605080

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

HM-30181 effectively blocked transepithelial transport of paclitaxel in MDCK monolayers (IC(50)=35.4nM)

Substance Class	Chemical Created by `admin` on `Sun Dec 18 05:15:23 UTC 2022` Edited by `admin` on `Sun Dec 18 05:15:23 UTC 2022`
Record UNII	2B3W09JOZR
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ENCEQUIDAR HYDROCHLORIDE

Common Name

English

HM-30181 MONOHYDROCHLORIDE SALT

Common Name

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-, MONOHYDROCHLORIDE

Common Name

English

HM-30181 HYDROCHLORIDE

Common Name

English

Code System Code Type Description

PUBCHEM

86278312

Created by admin on Sun Dec 18 05:15:23 UTC 2022 , Edited by admin on Sun Dec 18 05:15:23 UTC 2022

PRIMARY

CAS

849675-88-3

Created by admin on Sun Dec 18 05:15:23 UTC 2022 , Edited by admin on Sun Dec 18 05:15:23 UTC 2022

PRIMARY

FDA UNII

2B3W09JOZR

Created by admin on Sun Dec 18 05:15:23 UTC 2022 , Edited by admin on Sun Dec 18 05:15:23 UTC 2022

PRIMARY

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					K4I4I996O4

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ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/19903471 | http://www.athenex.com/oncology-innovation/oral-absorption-platform/oraxol-an-oral-formulation-of-paclitaxel/

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Cmax

AUC

T1/2

Doses

AEs

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19903471 | http://www.athenex.com/oncology-innovation/oral-absorption-platform/oraxol-an-oral-formulation-of-paclitaxel/

C_max

T_1/2