WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 532732
CAS#: 1416435-96-5
Description: GB-88 is a novel selective, orally available PAR2 antagonist.
MedKoo Cat#: 532732
Name: GB-88
CAS#: 1416435-96-5
Chemical Formula: C32H42N4O4
Exact Mass: 546.3206
Molecular Weight: 546.712
Elemental Analysis: C, 70.30; H, 7.74; N, 10.25; O, 11.71
Synonym: GB-88; GB 88; GB88;
IUPAC/Chemical Name: N-((S)-3-Cyclohexyl-1-(((2S,3S)-3-methyl-1-oxo-1-(spiro[indene-1,4'-piperidin]-1'-yl)pentan-2-yl)amino)-1-oxopropan-2-yl)isoxazole-5-carboxamide
InChi Key: DCUDDCGUKZLQLN-MCOVPRHSSA-N
InChi Code: InChI=1S/C32H42N4O4/c1-3-22(2)28(31(39)36-19-16-32(17-20-36)15-13-24-11-7-8-12-25(24)32)35-29(37)26(21-23-9-5-4-6-10-23)34-30(38)27-14-18-33-40-27/h7-8,11-15,18,22-23,26,28H,3-6,9-10,16-17,19-21H2,1-2H3,(H,34,38)(H,35,37)/t22-,26-,28-/m0/s1
SMILES Code: O=C(C1=CC=NO1)N[C@@H](CC2CCCCC2)C(N[C@@H]([C@@H](C)CC)C(N3CCC4(CC3)C=CC5=C4C=CC=C5)=O)=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: >3 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
| Biological target: | GB-88 is an oral, selective non-peptide antagonist of PAR2, inhibits PAR2 activated Ca2+ release with an IC50 of 2 µM. |
| In vitro activity: | When cells were pretreated with GB88 then stimulating with nTyr-p3 at 5µg/ml, the nTyr-p3-triggered Ca2+ release could be downregulated. Results indicated that the PAR-2 antagonist- GB88 is able to block PAR-2-mediated calcium signaling which inhibits the nTyr-p3-induced Ca2+ release (Figure 7C). In terms of Ca2+ release, the GB88 just behaved as a PAR-2 specific antagonist with no agonist activity. Reference: Front Immunol. 2021 Sep 8;12:557433. https://pubmed.ncbi.nlm.nih.gov/34566947/ |
| In vivo activity: | GB88 inhibited oedema induced by 2‐furoyl‐LIGRLO‐NH2 and reduced mechanical hyperalgesia by 30% (Figure 3A, B). Intraplantar injection of AC264613 induced a 10% increase in paw thickness at 1 h that persisted for 4 h (Figure 3C). AC264613 also evoked a robust mechanical hyperalgesia from 1 to 4 h (Figure 3D). GB88 prevented the proinflammatory and pronociceptive effects of AC264613 (Figure 3C, D). Thus, GB88 inhibits mouse paw inflammation and nociception caused by small molecule synthetic agonists of PAR2. Reference: Br J Pharmacol. 2016 Sep;173(18):2752-65. https://pubmed.ncbi.nlm.nih.gov/27423137/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 31.25 | 57.16 |
The following data is based on the product molecular weight 546.712 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.
| 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: | 1. Wang YJ, Yu SJ, Tsai JJ, Yu CH, Liao EC. Antagonism of Protease Activated Receptor-2 by GB88 Reduces Inflammation Triggered by Protease Allergen Tyr-p3. Front Immunol. 2021 Sep 8;12:557433. doi: 10.3389/fimmu.2021.557433. PMID: 34566947; PMCID: PMC8456102. 2. Suen JY, Cotterell A, Lohman RJ, Lim J, Han A, Yau MK, Liu L, Cooper MA, Vesey DA, Fairlie DP. Pathway-selective antagonism of proteinase activated receptor 2. Br J Pharmacol. 2014 Sep;171(17):4112-24. doi: 10.1111/bph.12757. Epub 2014 Jul 2. PMID: 24821440; PMCID: PMC4243983. 3. Lieu T, Savage E, Zhao P, Edgington-Mitchell L, Barlow N, Bron R, Poole DP, McLean P, Lohman RJ, Fairlie DP, Bunnett NW. Antagonism of the proinflammatory and pronociceptive actions of canonical and biased agonists of protease-activated receptor-2. Br J Pharmacol. 2016 Sep;173(18):2752-65. doi: 10.1111/bph.13554. Epub 2016 Aug 3. PMID: 27423137; PMCID: PMC4995288. |
| In vitro protocol: | 1. Wang YJ, Yu SJ, Tsai JJ, Yu CH, Liao EC. Antagonism of Protease Activated Receptor-2 by GB88 Reduces Inflammation Triggered by Protease Allergen Tyr-p3. Front Immunol. 2021 Sep 8;12:557433. doi: 10.3389/fimmu.2021.557433. PMID: 34566947; PMCID: PMC8456102. 2. Suen JY, Cotterell A, Lohman RJ, Lim J, Han A, Yau MK, Liu L, Cooper MA, Vesey DA, Fairlie DP. Pathway-selective antagonism of proteinase activated receptor 2. Br J Pharmacol. 2014 Sep;171(17):4112-24. doi: 10.1111/bph.12757. Epub 2014 Jul 2. PMID: 24821440; PMCID: PMC4243983. |
| In vivo protocol: | 1. Lieu T, Savage E, Zhao P, Edgington-Mitchell L, Barlow N, Bron R, Poole DP, McLean P, Lohman RJ, Fairlie DP, Bunnett NW. Antagonism of the proinflammatory and pronociceptive actions of canonical and biased agonists of protease-activated receptor-2. Br J Pharmacol. 2016 Sep;173(18):2752-65. doi: 10.1111/bph.13554. Epub 2016 Aug 3. PMID: 27423137; PMCID: PMC4995288. 2. Suen JY, Cotterell A, Lohman RJ, Lim J, Han A, Yau MK, Liu L, Cooper MA, Vesey DA, Fairlie DP. Pathway-selective antagonism of proteinase activated receptor 2. Br J Pharmacol. 2014 Sep;171(17):4112-24. doi: 10.1111/bph.12757. Epub 2014 Jul 2. PMID: 24821440; PMCID: PMC4243983. |
1. Wang YJ, Yu SJ, Tsai JJ, Yu CH, Liao EC. Antagonism of Protease Activated Receptor-2 by GB88 Reduces Inflammation
Triggered by Protease Allergen Tyr-p3. Front Immunol. 2021 Sep 8;12:557433. doi: 10.3389/fimmu.2021.557433. PMID: 34566947;
PMCID: PMC8456102.
2. Suen JY, Cotterell A, Lohman RJ, Lim J, Han A, Yau MK, Liu L, Cooper MA, Vesey DA, Fairlie DP. Pathway-selective
antagonism of proteinase activated receptor 2. Br J Pharmacol. 2014 Sep;171(17):4112-24. doi: 10.1111/bph.12757. Epub 2014 Jul 2.
PMID: 24821440; PMCID: PMC4243983.
3. Lieu T, Savage E, Zhao P, Edgington-Mitchell L, Barlow N, Bron R, Poole DP, McLean P, Lohman RJ, Fairlie DP, Bunnett NW.
Antagonism of the proinflammatory and pronociceptive actions of canonical and biased agonists of protease-activated receptor-2. Br J
Pharmacol. 2016 Sep;173(18):2752-65. doi: 10.1111/bph.13554. Epub 2016 Aug 3. PMID: 27423137; PMCID: PMC4995288.
