VU0119498
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MedKoo CAT#: 532894

CAS#: 79183-37-2

Description: VU0119498 is a M1 muscarinic receptor agonist (EC50 = 3.1 μM) and pan mAChR M3, M5 positive allosteric modulator (PAM). VU0119498 is a neuroprotective agent.


Chemical Structure

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VU0119498
CAS# 79183-37-2

Theoretical Analysis

MedKoo Cat#: 532894
Name: VU0119498
CAS#: 79183-37-2
Chemical Formula: C15H10BrNO2
Exact Mass: 314.9895
Molecular Weight: 316.15
Elemental Analysis: C, 56.99; H, 3.19; Br, 25.27; N, 4.43; O, 10.12

Price and Availability

Size Price Availability Quantity
50.0mg USD 250.0 2 Weeks
100.0mg USD 450.0 2 Weeks
200.0mg USD 750.0 2 Weeks
500.0mg USD 1550.0 2 Weeks
1.0g USD 2650.0 2 Weeks
2.0g USD 4650.0 2 Weeks
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Synonym: VU0119498, VU 0119498, VU-0119498

IUPAC/Chemical Name: 1-[(4-bromophenyl)methyl]indole-2,3-dione

InChi Key: DELLOEULSHGYCG-UHFFFAOYSA-N

InChi Code: InChI=1S/C15H10BrNO2/c16-11-7-5-10(6-8-11)9-17-13-4-2-1-3-12(13)14(18)15(17)19/h1-8H,9H2

SMILES Code: O=C1N(CC2=CC=C(Br)C=C2)C3=C(C=CC=C3)C1=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Product Data:

Biological target: VU0119498 is a M1 muscarinic receptor agonist (EC50 = 3.1 μM) and pan mAChR M3, M5 positive allosteric modulator (PAM).
In vitro activity: Functional HTS, identified VU0119498, which displayed micromolar potencies for potentiation of acetylcholine at M1, M3, and M5 receptors in cell-based Ca(2+) mobilization assays. Subsequent optimization led to the discovery of VU0238429, which possessed an EC(50) of approximately 1.16 microM at M5 with >30-fold selectivity versus M1 and M3, with no M2 or M4 potentiator activity. Reference: Bridges TM, Marlo JE, Niswender CM, Jones CK, Jadhav SB, Gentry PR, Plumley HC, Weaver CD, Conn PJ, Lindsley CW. Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins. J Med Chem. 2009 Jun 11;52(11):3445-8. doi: 10.1021/jm900286j. PMID: 19438238; PMCID: PMC3875304.
In vivo activity: In this study, VU0119498, a drug known to act as a PAM at M3Rs, significantly augmented ACh-induced insulin release from cultured β cells and mouse and human pancreatic islets. This stimulatory effect was absent in islets prepared from mice lacking M3Rs, indicative of the involvement of M3Rs. VU0119498 treatment of wild-type mice caused a significant increase in plasma insulin levels, accompanied by a striking improvement in glucose tolerance. These effects were mediated by β-cell M3Rs, since they were absent in mutant mice selectively lacking M3Rs in β cells. Moreover, acute VU0119498 treatment of obese, glucose-intolerant mice triggered enhanced insulin release and restored normal glucose tolerance. Interestingly, doses of VU0119498 that led to pronounced improvements in glucose homeostasis did not cause any significant side effects due to activation of M3Rs expressed by other peripheral cell types. Taken together, the data from this proof-of-concept study strongly suggest that M3R PAMs may become clinically useful as novel antidiabetic agents. Reference: Zhu L, Rossi M, Cohen A, Pham J, Zheng H, Dattaroy D, Mukaibo T, Melvin JE, Langel JL, Hattar S, Matschinsky FM, Appella DH, Doliba NM, Wess J. Allosteric modulation of β-cell M3 muscarinic acetylcholine receptors greatly improves glucose homeostasis in lean and obese mice. Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18684-18690. doi: 10.1073/pnas.1904943116. Epub 2019 Aug 26. PMID: 31451647; PMCID: PMC6744902.

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 158.15

Preparing Stock Solutions

The following data is based on the product molecular weight 316.15 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: Bridges TM, Marlo JE, Niswender CM, Jones CK, Jadhav SB, Gentry PR, Plumley HC, Weaver CD, Conn PJ, Lindsley CW. Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins. J Med Chem. 2009 Jun 11;52(11):3445-8. doi: 10.1021/jm900286j. PMID: 19438238; PMCID: PMC3875304.
In vitro protocol: Bridges TM, Marlo JE, Niswender CM, Jones CK, Jadhav SB, Gentry PR, Plumley HC, Weaver CD, Conn PJ, Lindsley CW. Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins. J Med Chem. 2009 Jun 11;52(11):3445-8. doi: 10.1021/jm900286j. PMID: 19438238; PMCID: PMC3875304.
In vivo protocol: Zhu L, Rossi M, Cohen A, Pham J, Zheng H, Dattaroy D, Mukaibo T, Melvin JE, Langel JL, Hattar S, Matschinsky FM, Appella DH, Doliba NM, Wess J. Allosteric modulation of β-cell M3 muscarinic acetylcholine receptors greatly improves glucose homeostasis in lean and obese mice. Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18684-18690. doi: 10.1073/pnas.1904943116. Epub 2019 Aug 26. PMID: 31451647; PMCID: PMC6744902.

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1: Bridges TM, Kennedy JP, Hopkins CR, Conn PJ, Lindsley CW. Heterobiaryl and heterobiaryl ether derived M5 positive allosteric modulators. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5617-22. doi: 10.1016/j.bmcl.2010.08.042. Epub 2010 Aug 12. PubMed PMID: 20801651; PubMed Central PMCID: PMC3179183.

2: Bridges TM, Phillip Kennedy J, Noetzel MJ, Breininger ML, Gentry PR, Conn PJ, Lindsley CW. Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM. Bioorg Med Chem Lett. 2010 Mar 15;20(6):1972-5. doi: 10.1016/j.bmcl.2010.01.109. Epub 2010 Feb 1. PubMed PMID: 20156687; PubMed Central PMCID: PMC2834874.

3: Bridges TM, Kennedy JP, Cho HP, Breininger ML, Gentry PR, Hopkins CR, Conn PJ, Lindsley CW. Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM. Bioorg Med Chem Lett. 2010 Jan 15;20(2):558-62. doi: 10.1016/j.bmcl.2009.11.089. Epub 2009 Nov 22. PubMed PMID: 20004578; PubMed Central PMCID: PMC3177601.

4: Bridges TM, Marlo JE, Niswender CM, Jones CK, Jadhav SB, Gentry PR, Plumley HC, Weaver CD, Conn PJ, Lindsley CW. Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins. J Med Chem. 2009 Jun 11;52(11):3445-8. doi: 10.1021/jm900286j. PubMed PMID: 19438238; PubMed Central PMCID: PMC3875304.