MDL-29951CAS# 130798-51-5 |
- Acetyl-Calpastatin (184-210) (human)
Catalog No.:BCC2350
CAS No.:123714-50-1
- CA 074
Catalog No.:BCC1141
CAS No.:134448-10-5
- PD 151746
Catalog No.:BCC5485
CAS No.:179461-52-0
- Odanacatib (MK-0822)
Catalog No.:BCC1197
CAS No.:603139-19-1
- E-64-c
Catalog No.:BCC3588
CAS No.:76684-89-4
- SID 26681509
Catalog No.:BCC2362
CAS No.:958772-66-2
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 130798-51-5 | SDF | Download SDF |
PubChem ID | 446916 | Appearance | Powder |
Formula | C12H9Cl2NO4 | M.Wt | 302.11 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : ≥ 50 mg/mL (165.50 mM) *"≥" means soluble, but saturation unknown. | ||
Chemical Name | 3-(2-carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid | ||
SMILES | C1=C(C=C2C(=C1Cl)C(=C(N2)C(=O)O)CCC(=O)O)Cl | ||
Standard InChIKey | KNBSYZNKEAWABY-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C12H9Cl2NO4/c13-5-3-7(14)10-6(1-2-9(16)17)11(12(18)19)15-8(10)4-5/h3-4,15H,1-2H2,(H,16,17)(H,18,19) | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Potent, selective antagonist at the glycine-NMDA site (IC50 = 140 nM against glycine binding). Displays 2500-fold selectivity for the glycine vs. glutamate binding site. |
MDL-29951 Dilution Calculator
MDL-29951 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 3.3101 mL | 16.5503 mL | 33.1005 mL | 66.2011 mL | 82.7513 mL |
5 mM | 0.662 mL | 3.3101 mL | 6.6201 mL | 13.2402 mL | 16.5503 mL |
10 mM | 0.331 mL | 1.655 mL | 3.3101 mL | 6.6201 mL | 8.2751 mL |
50 mM | 0.0662 mL | 0.331 mL | 0.662 mL | 1.324 mL | 1.655 mL |
100 mM | 0.0331 mL | 0.1655 mL | 0.331 mL | 0.662 mL | 0.8275 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
MDL-29951 is a novel glycine antagonist of NMDA receptor activation (Ki=0.14 mM, [3H]glycine binding) in vitro and in vivo.
- 6-O-benzoylgomisin O
Catalog No.:BCN3092
CAS No.:130783-32-3
- m-CPP hydrochloride
Catalog No.:BCC5680
CAS No.:13078-15-4
- Decloxizine dihydrochloride
Catalog No.:BCC5549
CAS No.:13073-96-6
- FR 122047 hydrochloride
Catalog No.:BCC7092
CAS No.:130717-51-0
- SDZ WAG 994
Catalog No.:BCC7374
CAS No.:130714-47-5
- (R)-(+)-Propranolol hydrochloride
Catalog No.:BCC6810
CAS No.:13071-11-9
- Dorzolamide HCl
Catalog No.:BCC2311
CAS No.:130693-82-2
- RP 001 hydrochloride
Catalog No.:BCC7905
CAS No.:1306761-53-4
- Ozanimod (RPC1063)
Catalog No.:BCC6533
CAS No.:1306760-87-1
- PD123319
Catalog No.:BCC5010
CAS No.:130663-39-7
- Bindarit
Catalog No.:BCC4965
CAS No.:130641-38-2
- N-(2-Hydroxyethyl)-3-(4-nitrophenyl)propylamine
Catalog No.:BCC9053
CAS No.:130634-09-2
- Sipatrigine
Catalog No.:BCC7847
CAS No.:130800-90-7
- Pseudolarifuroic acid
Catalog No.:BCN8048
CAS No.:130825-79-5
- 7-Oxohinokinin
Catalog No.:BCN6162
CAS No.:130837-92-2
- Scoparinol
Catalog No.:BCN6163
CAS No.:130838-00-5
- Decursinol angelate
Catalog No.:BCC9222
CAS No.:130848-06-5
- ent-kaurane-3,16,17-triol
Catalog No.:BCN6164
CAS No.:130855-22-0
- 1beta,10beta-Epoxydehydroleucodin
Catalog No.:BCN7331
CAS No.:130858-00-3
- Fmoc-Val-OSu
Catalog No.:BCC3572
CAS No.:130878-68-1
- N4-Benzoylcytidine
Catalog No.:BCC9072
CAS No.:13089-48-0
- 7-O-Acetylneocaesalpin N
Catalog No.:BCN7332
CAS No.:1309079-08-0
- Entacapone
Catalog No.:BCC2217
CAS No.:130929-57-6
- CX-4945 sodium salt
Catalog No.:BCC5586
CAS No.:1309357-15-0
The Orphan G Protein-coupled Receptor GPR17 Negatively Regulates Oligodendrocyte Differentiation via Galphai/o and Its Downstream Effector Molecules.[Pubmed:26620557]
J Biol Chem. 2016 Jan 8;291(2):705-18.
Recent studies have recognized G protein-coupled receptors as important regulators of oligodendrocyte development. GPR17, in particular, is an orphan G protein-coupled receptor that has been identified as oligodendroglial maturation inhibitor because its stimulation arrests primary mouse oligodendrocytes at a less differentiated stage. However, the intracellular signaling effectors transducing its activation remain poorly understood. Here, we use Oli-neu cells, an immortalized cell line derived from primary murine oligodendrocytes, and primary rat oligodendrocyte cultures as model systems to identify molecular targets that link cell surface GPR17 to oligodendrocyte maturation blockade. We demonstrate that stimulation of GPR17 by the small molecule agonist MDL29,951 (2-carboxy-4,6-dichloro-1H-indole-3-propionic acid) decreases myelin basic protein expression levels mainly by triggering the Galphai/o signaling pathway, which in turn leads to reduced activity of the downstream cascade adenylyl cyclase-cAMP-PKA-cAMP response element-binding protein (CREB). In addition, we show that GPR17 activation also diminishes myelin basic protein abundance by lessening stimulation of the exchange protein directly activated by cAMP (EPAC), thus uncovering a previously unrecognized role for EPAC to regulate oligodendrocyte differentiation. Together, our data establish PKA and EPAC as key downstream effectors of GPR17 that inhibit oligodendrocyte maturation. We envisage that treatments augmenting PKA and/or EPAC activity represent a beneficial approach for therapeutic enhancement of remyelination in those demyelinating diseases where GPR17 is highly expressed, such as multiple sclerosis.
3-(2-carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid: an allosteric inhibitor of fructose-1,6-bisphosphatase at the AMP site.[Pubmed:12781194]
Bioorg Med Chem Lett. 2003 Jun 16;13(12):2055-8.
3-(2-Carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid (MDL-29951), an antagonist of the glycine site of the NMDA receptor, has been found to be an allosteric inhibitor of the enzyme fructose 1,6-bisphosphatase. The compound binds at the AMP regulatory site by X-ray crystallography. This represents a new approach to inhibition of fructose 1,6-bisphosphatase and serves as a lead for further drug design.
Blockade of NMDA receptors in the nucleus accumbens elicits spontaneous tail-flicks in rats.[Pubmed:10657545]
Eur J Pharmacol. 2000 Jan 24;388(1):37-47.
The open channel blocker at N-methyl-D-aspartate (NMDA) receptors, dizocilpine, stereospecifically elicited spontaneous tail-flicks in rats - a reaction similar to those elicited by other drugs (tenocyclidine, phencyclidine and ketamine) acting as open channel blockers. Their relative potencies were strongly correlated with affinities at NMDA binding sites and labeled by [3H]dizocilpine in the frontal cortex (r=0.94) and, as determined previously [Millan, M. J., Seguin, L., 1994. Chemically-diverse ligands at the glycine B site coupled to N-methyl-D-aspartate (NMDA) receptors selectively block the late phase of formalin-induced pain in mice, Neurosci. Lett., 178 (1994) 139-143], potency for eliciting antinociception (0. 93). The competitive antagonists at the NMDA receptor recognition site, (+/-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), 4-phosphonomethyl-2-piperidine carboxylic acid (CGS19755), D, L-(E)-2-amino-4-methylphosphono-3-pentanoic acid (CGP37849) and (3E)-1-ethyl ester-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP39551), likewise dose-dependently evoked spontaneous tail-flick. In contrast, antagonists/weak partial agonists at the coupled, glycine B site, 7-chloro-4-hydroxy-3-(3-phenoxy) phenyl-2(H)-quinolinone (L701,324), (+)-1-hydroxy-3-aminopyrrolidine-2-one ((+)-HA966), (3R, 4R)-3-amino-1-hydroxy-4-methyl-2-pyrrolidinone (L687,414), 6, 7-dichloro-1, 4-dihydro-5-nitro, 2,3 quinoxalinedione (ACEA1021) and 2-carboxy-4,6-dichloro (1H)-indole-3-propanoic acid (MDL29,951), were inactive. NMDA abolished induction of spontaneous tail-flick by CPP and CGS19755, but not by dizocilpine. Upon bilateral injection into the nucleus accumbens, dizocilpine immediately and dose-dependently elicited spontaneous tail-flick, but it was ineffective in the ventrotegmental area and striatum. Similarly, injection of CPP into the nucleus accumbens elicited spontaneous tail-flick. Neither dizocilpine nor CPP elicited spontaneous tail-flick upon administration onto lumbar spinal cord. In conclusion, a pharmacologically specific spontaneous tail-flick-response is elicited by both open channel blockers and recognition site antagonists, but not glycine B site antagonists, at NMDA receptors. Their actions, mediated in the nucleus accumbens, may be differentiated by their respective resistance and sensitivity to NMDA.
Decoding signaling and function of the orphan G protein-coupled receptor GPR17 with a small-molecule agonist.[Pubmed:24150254]
Sci Signal. 2013 Oct 22;6(298):ra93.
Replacement of the lost myelin sheath is a therapeutic goal for treating demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis (MS). The G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) GPR17, which is phylogenetically closely related to receptors of the "purinergic cluster," has emerged as a modulator of CNS myelination. However, whether GPR17-mediated signaling positively or negatively regulates this critical process is unresolved. We identified a small-molecule agonist, MDL29,951, that selectively activated GPR17 even in a complex environment of endogenous purinergic receptors in primary oligodendrocytes. MDL29,951-stimulated GPR17 engaged the entire set of intracellular adaptor proteins for GPCRs: G proteins of the Galpha(i), Galpha(s), and Galpha(q) subfamily, as well as beta-arrestins. This was visualized as alterations in the concentrations of cyclic adenosine monophosphate and inositol phosphate, increased Ca(2)(+) flux, phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), as well as multifeatured cell activation recorded with label-free dynamic mass redistribution and impedance biosensors. MDL29,951 inhibited the maturation of primary oligodendrocytes from heterozygous but not GPR17 knockout mice in culture, as well as in cerebellar slices from 4-day-old wild-type mice. Because GPCRs are attractive targets for therapeutic intervention, inhibiting GPR17 emerges as therapeutic strategy to relieve the oligodendrocyte maturation block and promote myelin repair in MS.
The glycine site of the NMDA receptor contributes to neurokinin1 receptor agonist facilitation of NMDA receptor agonist-evoked activity in rat dorsal horn neurons.[Pubmed:9027383]
Brain Res. 1997 Jan 9;744(2):235-45.
We have investigated the role of the glycine recognition site of the N-methyl-D-aspartate receptor (the GlyNMDA site) in the facilitation of NMDA receptor agonist-evoked activity in rat dorsal horn neurons that is brought about by neurokinin1 (NK1) receptor agonist and the contribution of protein kinase C (PKC) activation to this phenomenon. Ionophoresis of the selective NMDA receptor agonist 1-aminocyclobutane-cis-1,3-dicarboxylic acid (ACBD) produced a sustained increase in the firing rate of single laminae III-V neurons recorded extracellularly using multibarrelled glass electrodes. The highly selective NK1 receptor agonist acetyl-[Arg6,Sar9,Met(O2)11]-SP6-11 (Sar9-SP) greatly facilitated this response, but under the present conditions had no effect when applied alone or with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonist) at the same current. In the presence of the GLyNMDA site antagonists 2-carboxy-4,6-dichloro-(1H)-indole-3-propanoic acid (MDL 29951), 7-chloro-3-(cyclopropylcarbonyl)-4-hydroxy-2(1H)-quinoline (L701,252), 5,7-dinitroquinaxoline-2,3-dione (MNQX) or 7-chlorothiokynurenic acid (7-CTK), or the PKC inhibitors, chelerythrine or GF109203X, the Sar9-SP-induced facilitation of ACBD-evoked activity was prevented, generally restoring activity to a level similar to that in the presence of ACBD alone, whilst an AMPA receptor antagonist, 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione (NBQX) did not inhibit the facilitation. At the same ionophoretic currents these compounds had no effect on ACBD-evoked activity in the absence of Sar9-SP but were inhibitory at significantly greater currents. To further substantiate the importance of the GlyNMDA site in the interaction, the effects of NMDA receptor antagonists selective for alternative recognition sites on the NMDA receptor were investigated. MK-801, a non-competitive NMDA receptor antagonist and arcaine, a competitive inhibitor at the polyamine site, were applied to the facilitated activity seen in the presence of Sar9-SP and ACBD, and to ACBD-evoked activity alone. Unlike the GlyNMDA site antagonists and PKC inhibitors, these compounds reduced both facilitated and ACBD-evoked activity at similar currents. Furthermore, like the NK1 receptor agonist, a selective GlyNMDA site agonist 1-aminocyclopropane carboxylic acid (ACPC) caused facilitation of ACBD-evoked activity which was also blocked by currents of L701,252 that did not alter activity evoked by ACBD alone. These data suggest that activation of the GlyNMDA site (perhaps as a consequence of glycine release or modification of its influence by intracellular signalling cascades) is an essential component of the means by which NK1 receptor activation results in facilitated responsiveness of dorsal horn neurons towards NMDA receptor agonists.