[CAS NO. 1449746-00-2] Mefuparibhydrochloride
PRODUCTS SPECIFICATIONS [1449746-00-2]
DESCRIPTION [1449746-00-2]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 334.77 |
| Molecular Formula | C17H16ClFN2O2 |
| SMILES | O=C(C1=C(OC(C2=CC=C(CNC)C=C2)=C3)C3=CC(F)=C1)N.[H]Cl |
Summary
IC50 & Target
|
PARP1 3.2 nM (IC 50 ) |
PARP2 1.9 nM (IC 50 ) |
TNKS1 1.6 μM (IC 50 ) |
TNKS2 1.3 μM (IC 50 ) |
In Vitro
Mefuparib hydrochloride (1-10 μM; 48 hours) causes cell apoptosis
[1]
.
Mefuparib hydrochloride (MPH; 1-10 μM; 24 hours) causes V-C8 cells into typical G2/M arrest
[1]
.
Mefuparib hydrochloride (1-10 μM; 24 hours) causes the accumulation of DSB marked by the increased levels of γH2AX in the MDA-MB-436 (BRCA1
−/−
) cells in a concentration-dependent manner
[1]
.
Mefuparib hydrochloride exerts potent in vitro proliferation-inhibitory effects on cancer cells derived from different human tissues with an average IC
50
of 2.16 μM (0.12 μM~3.64 μM)
[1]
.
Mefuparib hydrochloride inhibits PARP3 (IC
50
>10 μM), PARP6 (IC
50
>10 μM), TNKS1 (IC
50
=1.6 μM), TNKS2 (IC
50
=1.3 μM)
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Apoptosis Analysis [1]
| Cell Line: | V-C8 cells |
| Concentration: | 1, 3, 10 μM |
| Incubation Time: | 48 hours |
| Result: | Caused cell apoptosis. |
Cell Cycle Analysis [1]
| Cell Line: | V-C8 cells |
| Concentration: | 1, 3, 10 μM |
| Incubation Time: | 24 hours |
| Result: | Cell came into typical G2/M arrest. |
Western Blot Analysis [1]
| Cell Line: | MDA-MB-436 (BRCA1 −/− ) cells |
| Concentration: | 1, 10 μM |
| Incubation Time: | 24 hours |
| Result: | Caused the accumulation of DSB marked by the increased levels of γH2AX in the MDA-MB-436 (BRCA1 −/− ) cells in a concentration-dependent manner. |
In Vivo
Mefuparib hydrochloride (MPH; 40-160 mg/kg; orally; once every other day; for 21 days) displays dose- and time-dependent killing on V-C8 xenografts accompanied by complete disappearance of some xenografts, especially in the high-dose group
[1]
.
Mefuparib hydrochloride (160 mg/kg; orally; once every other day; for 21 days) inhibits the growth of the BR-05-0028 breast patient-derived xenograft (PDX) without obvious loss of body weight
[1]
.
Mefuparib hydrochloride (10, 20, 40 mg/kg; oral) has a T
1/2
of 1.07-1.3 hours and a C
max
of 116-725 ng/mL for SD rats
[1]
.
Mefuparib hydrochloride (5, 10, 20 mg/kg; oral) has a T
1/2
of 2.16-2.7 hours and a C
max
of 114-608 ng/mL for cynomolgus monkeys
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Nude mice with V-C8 xenografts [1] |
| Dosage: | 40, 80, 160 mg/kg |
| Administration: | Orally; once every other day; for 21 days |
| Result: | Displayed dose- and time-dependent killing on V-C8 xenografts accompanied by complete disappearance of some xenografts, especially in the high-dose group. |
| Animal Model: | SD rats [1] |
| Dosage: | 10, 20, 40 mg/kg (Pharmacokinetic Analysis) |
| Administration: | Oral |
| Result: | Had a T 1/2 of 1.07-1.3 hours and a C max of 116-725 ng/mL. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT04113551 | Janssen Research & Development, LLC |
Attention Deficit Disorder With Hyperactivity
|
October 1, 2019 | |
| NCT01065259 | Peking University |
Attention Deficit Hyperactivity Disorder
|
April 2008 | Phase 4 |
| NCT00602290 | University of California, Los Angeles|National Institute of Mental Health (NIMH) |
Depression
|
February 2008 | Phase 4 |
| NCT02695355 | Ostfold Hospital Trust |
Attention Deficit Hyperactivity Disorder
|
October 2006 | Phase 2 |
| NCT02493777 | Ironshore Pharmaceuticals and Development, Inc |
Attention Deficit Hyperactivity Disorder
|
July 2015 | Phase 3 |
| NCT02020200 | Shalvata Mental Health Center |
BD
|
January 2014 | Not Applicable |
| NCT02778360 | Mensia Technologies SA|European Union H2020 SME Instrument |
Attention Deficit-Hyperactivity Disorder
|
August 2016 | Phase 1|Phase 2 |
| NCT05229627 | Peking University Sixth Hospital|Hangzhou Normal University |
ADHD
|
January 2016 | |
| NCT03669796 | Helse Møre og Romsdal HF|Haukeland University Hospital |
Healthy Volunteers
|
November 27, 2017 | Not Applicable |
| NCT03709940 | King´s College London|Shire |
Attention Deficit Hyperactivity Disorder (ADHD)
|
May 3, 2013 | Not Applicable |
| NCT00429273 | University of California, Los Angeles|National Institute of Mental Health (NIMH) |
Attention Deficit Disorder With Hyperactivity
|
January 2007 | Phase 4 |
| NCT04283604 | Loewenstein Hospital|Tel Aviv University|Wingate Institute |
ADHD
|
May 27, 2021 | Phase 4 |
| NCT03647930 | Memorial Health University Medical Center |
Seroma
|
May 15, 2012 | Not Applicable |
| NCT01673594 | Massachusetts General Hospital|United States Department of Defense |
ADHD|Stimulant-Induced Euphoria
|
September 2012 | Phase 4 |
| NCT00937040 | Ortho-McNeil Janssen Scientific Affairs, LLC |
Attention Deficit Disorder With Hyperactivity
|
July 2009 | Phase 4 |
| NCT01683032 | Shalvata Mental Health Center |
MPH Influence on Creativity
|
October 2012 | Not Applicable |
| NCT02520388 | Ironshore Pharmaceuticals and Development, Inc |
Attention Deficit Hyperactivity Disorder
|
August 2015 | Phase 3 |
| NCT03358277 | Tri-Service General Hospital|Ministry of Science and Technology, Taiwan |
Disruptive Mood Dysregulation Disorder
|
November 19, 2014 | Not Applicable |
| NCT02293655 | Children´s Hospital Medical Center, Cincinnati|Seattle Children´s Hospital |
ADHD
|
January 12, 2015 | Phase 4 |
| NCT02754258 | Children´s Hospital of Eastern Ontario|University of Ottawa |
Obesity
|
January 2017 | Phase 3 |
| NCT02430896 | Asan Medical Center |
Attention Deficit Disorder With Hyperactivity
|
February 2015 | |
| NCT04799379 | Grupo Español de Rehabilitación Multimodal|Universidad de Zaragoza|Aragon Health Science Institute |
Postoperative Sepsis
|
April 1, 2021 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 25 mg/mL ( 74.68 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.9871 mL | 14.9356 mL | 29.8713 mL |
| 5 mM | 0.5974 mL | 2.9871 mL | 5.9743 mL |
| 10 mM | 0.2987 mL | 1.4936 mL | 2.9871 mL |
References
- [1] He JX, et al. Novel PARP1/2 inhibitor mefuparib hydrochloride elicits potent in vitro and in vivo anticancer activity, characteristic of high tissue distribution. Oncotarget. 2017 Jan 17;8(3):4156-4168.
- [2] Nie D, et al. Cancer-Cell-Membrane-Coated Nanoparticles with a Yolk-Shell Structure Augment Cancer Chemotherapy. Nano Lett. 2020 Feb 12;20(2):936-946.