BMS-767778
BMS-767778 is an orally active and selective DPP4 inhibitor with Ki values of 0.94 nM, 4.9, 3.2 nM for DPP4, DPP8 and DPP9 respectively. BMS-767778 exhibits >3,000-fold selectivity over the related enzymes DPP8 and DPP9. BMS-767778 inhibits CYP-3A4 with IC50 of 5.2 μM. BMS-767778 significantly reduces blood glucose levels in high fat fed (HFD) ob/ob mice with safety profile. BMS-767778 can be used for diabetes mellitus research.
For research use only. We do not sell to patients.
- CAS No.: 915729-95-2
- Formula: C19H20Cl2N4O2
- Molecular Weight:407.29
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
DPP-4 0.94 μM (Ki) |
DPP-8 4.9 nM (Ki) |
DPP-9 3.2 nM (Ki) |
In Vitro
BMS-767778 (compound 2s) exhibits good passive membrane permeability, with PAMPA effective permeability (Pe) values of 19.7, 129.7, and 330 × 10-6 cm/s at pH 5.5, 6.5, and 7.4, respectively[1].
BMS-767778 displays an efflux ratio (basolateral-to-apical / apical-to-basolateral permeability) of greater than 5 in Caco-2 cell assays (at pH > 6.5)[1].
BMS-767778 exhibits low plasma protein binding across species: 18% (human), 14% (mouse), 28% (rat), 27% (dog), and 16% (monkey) [1].
BMS-767778 demonstrates a low metabolic turnover in both liver microsomes and hepatocytes, and correspondingly, a low hepatic clearance is predicted in humans[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
BMS-767778 (500 mg/kg, o.p., once) results no clinical chemistry or hemotology changes in rats[1].
BMS-767778 (300 mg/kg, o.p., 14 days) results no clinical chemistry or hemotology changes in rats[1].
BMS-767778 (25 mg/kg, o.p., 5 days) produces no significant changes in dogs[1].
BMS-767778 (50 mg/kg, o.p., 5 days) results a softening of stools in dog[1].
BMS-767778 (50 mg/kg) not demonstrate any potential for undesirable cardiovascular activity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 915729-95-2
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Molecular Weight 407.29
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Formula C19H20Cl2N4O2
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SMILES
O=C(N(C)C)CN1CC2=NC(C)=C(CN)[C@]([C@]3=CC=C(Cl)C=C3Cl)=C2C1=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Research Protocol for Metabolic Diseases
AMP-activated protein kinase, AMPK, is a conserved cellular energy sensor that responds to reduced cellular energy status and coordinates metabolism by increasing ATP-generating catabolic pathways while suppressing ATP-consuming anabolic processes. In metabolic disease research, the AMPK pathway is experimentally relevant because it regulates hepatic lipid synthesis, fatty acid oxidation, glucose production, skeletal-muscle glucose disposal, mTORC1-linked biosynthesis, autophagy, mitochondrial homeostasis, and whole-body energy balance. The central pathway logic is that energy stress, metformin, exercise-like stimulation, or direct AMPK activators increase AMPKα Thr172 phosphorylation and downstream substrate phosphorylation, including ACC and RAPTOR. Phosphorylation of ACC suppresses lipogenesis and supports fatty acid oxidation, whereas phosphorylation of RAPTOR suppresses mTORC1 signaling and links cellular energy status to growth and protein synthesis control. The pathway is linked
Purity & Documentation
References
[1]. Pratik Devasthale, et al. Optimization of activity, selectivity, and liability profiles in 5-oxopyrrolopyridine DPP4 inhibitors leading to clinical candidate (Sa)-2-(3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778). J Med Chem . 2013 Sep 26;56(18):7343-57. [Content Brief]
[2]. Devasthale P, et al, Hamann LG. Optimization of activity, selectivity, and liability profiles in 5-oxopyrrolopyridine DPP4 inhibitors leading to clinical candidate (Sa)-2-(3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778). J Med Chem. 2013 Sep 26;56(18):7343-57. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
BMS-767778 Related Classifications
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