GGTI 2133 | CAS#191102-79-1 | GGTase I inhibitor

MedKoo Cat#: 555193 | Name: GGTI-2133

Featured

Description:

WARNING: This product is for research use only, not for human or veterinary use.

GGTI-2133 is a peptidomimetic inhibitor of geranylgeranyl transferase type I (GGTase I; IC50 = 38 nM). GGTI-2133 inhibits infiltration of inflammatory cells into airways in mouse experimental asthma. GGTI-2133 increase erythrocyte deformability but reduce low O(2) tension-induced ATP release.

Chemical Structure

GGTI-2133

CAS#191102-79-1

Theoretical Analysis

MedKoo Cat#: 555193

Name: GGTI-2133

CAS#: 191102-79-1

Chemical Formula: C27H28N4O3

Exact Mass: 456.2161

Molecular Weight: 456.55

Elemental Analysis: C, 71.03; H, 6.18; N, 12.27; O, 10.51

Price and Availability

Size	Price	Availability	Quantity
1mg	USD 450.00	2 Weeks
5mg	USD 1,250.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

GGTI 2133; GGTI-2133; GGTI2133.

IUPAC/Chemical Name

N-[4-[(1H-imidazol-5-ylmethyl)amino]-2-(1-naphthalenyl)benzoyl]-L-leucine

InChi Key

ODTFPKNIFYMEHP-VWLOTQADSA-N

InChi Code

InChI=1S/C27H28N4O3/c1-17(2)12-25(27(33)34)31-26(32)23-11-10-19(29-15-20-14-28-16-30-20)13-24(23)22-9-5-7-18-6-3-4-8-21(18)22/h3-11,13-14,16-17,25,29H,12,15H2,1-2H3,(H,28,30)(H,31,32)(H,33,34)/t25-/m0/s1

SMILES Code

CC(C)C[C@@H](C(O)=O)NC(C1=CC=C(NCC2=CN=CN2)C=C1C3=C4C=CC=CC4=CC=C3)=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

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

GGTI-2133 is a peptidomimetic inhibitor of geranylgeranyl transferase type I (GGTase I; IC50 = 38 nM).

In vitro activity:

Simvastatin treatment increased rat erythrocyte deformability compared with controls (n = 6, P < 0.05). However, erythrocytes of simvastatin-treated rats (n = 9, P < 0.05) exhibited impaired low O2 tension-induced ATP release. Similarly, the geranylgeranyl transferase inhibitor GGTI-2133 (10 μM) also increased deformability and impaired low O2 tension-induced ATP release in healthy human erythrocytes (P < 0.05). Reference: Am J Physiol Heart Circ Physiol. 2013 Mar 1;304(5):H660-6. https://pubmed.ncbi.nlm.nih.gov/23335799/

In vivo activity:

Administration of GGTI-2133 reduced Mac-1 expression on peripheral blood neutrophils in septic mice (Fig. 3, A and B, P < 0.05 vs. Vehicle + CLP, n = 5). Thus mean fluorescence intensity values of Mac-1 on neutrophils decreased from 336.4 ± 17.6 to 189.6 ± 11.5 in CLP mice pretreated with GGTI-2133 (10 mg/kg), which corresponds to an 84% reduction (Fig. 3, A and B). Reference: Am J Physiol Lung Cell Mol Physiol. 2013 Feb 15;304(4):L221-9. https://pubmed.ncbi.nlm.nih.gov/23241528/

Preparing Stock Solutions

The following data is based on the product molecular weight 456.55 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. Abdullah MI, Abed MN, Richardson A. Inhibition of the mevalonate pathway augments the activity of pitavastatin against ovarian cancer cells. Sci Rep. 2017 Aug 14;7(1):8090. doi: 10.1038/s41598-017-08649-9. PMID: 28808351; PMCID: PMC5556066. 2. Clapp KM, Ellsworth ML, Sprague RS, Stephenson AH. Simvastatin and GGTI-2133, a geranylgeranyl transferase inhibitor, increase erythrocyte deformability but reduce low O(2) tension-induced ATP release. Am J Physiol Heart Circ Physiol. 2013 Mar 1;304(5):H660-6. doi: 10.1152/ajpheart.00635.2012. Epub 2013 Jan 18. PMID: 23335799; PMCID: PMC3602752. 3. Hasan Z, Rahman M, Palani K, Syk I, Jeppsson B, Thorlacius H. Geranylgeranyl transferase regulates CXC chemokine formation in alveolar macrophages and neutrophil recruitment in septic lung injury. Am J Physiol Lung Cell Mol Physiol. 2013 Feb 15;304(4):L221-9. doi: 10.1152/ajplung.00199.2012. Epub 2012 Dec 14. PMID: 23241528. 4. Chiba Y, Sato S, Misawa M. GGTI-2133, an inhibitor of geranylgeranyltransferase, inhibits infiltration of inflammatory cells into airways in mouse experimental asthma. Int J Immunopathol Pharmacol. 2009 Oct-Dec;22(4):929-35. doi: 10.1177/039463200902200408. PMID: 20074456.

In vitro protocol:

In vivo protocol:

1. Hasan Z, Rahman M, Palani K, Syk I, Jeppsson B, Thorlacius H. Geranylgeranyl transferase regulates CXC chemokine formation in alveolar macrophages and neutrophil recruitment in septic lung injury. Am J Physiol Lung Cell Mol Physiol. 2013 Feb 15;304(4):L221-9. doi: 10.1152/ajplung.00199.2012. Epub 2012 Dec 14. PMID: 23241528. 2. Chiba Y, Sato S, Misawa M. GGTI-2133, an inhibitor of geranylgeranyltransferase, inhibits infiltration of inflammatory cells into airways in mouse experimental asthma. Int J Immunopathol Pharmacol. 2009 Oct-Dec;22(4):929-35. doi: 10.1177/039463200902200408. PMID: 20074456.

1: Abdullah MI, Abed MN, Richardson A. Inhibition of the mevalonate pathway augments the activity of pitavastatin against ovarian cancer cells. Sci Rep. 2017 Aug 14;7(1):8090. doi: 10.1038/s41598-017-08649-9. PubMed PMID: 28808351; PubMed Central PMCID: PMC5556066. 2: Vilimanovich U, Bosnjak M, Bogdanovic A, Markovic I, Isakovic A, Kravic-Stevovic T, Mircic A, Trajkovic V, Bumbasirevic V. Statin-mediated inhibition of cholesterol synthesis induces cytoprotective autophagy in human leukemic cells. Eur J Pharmacol. 2015 Oct 15;765:415-28. doi: 10.1016/j.ejphar.2015.09.004. Epub 2015 Sep 8. PubMed PMID: 26358205. 3: Hui KP, Kuok DI, Kang SS, Li HS, Ng MM, Bui CH, Peiris JS, Chan RW, Chan MC. Modulation of sterol biosynthesis regulates viral replication and cytokine production in influenza A virus infected human alveolar epithelial cells. Antiviral Res. 2015 Jul;119:1-7. doi: 10.1016/j.antiviral.2015.04.005. Epub 2015 Apr 13. PubMed PMID: 25882623. 4: Ohsawa M, Mutoh J, Yamamoto S, Hisa H. Involvement of protein isoprenylation in neuropathic pain induced by sciatic nerve injury in mice. Neurosci Lett. 2014 Apr 3;564:27-31. doi: 10.1016/j.neulet.2014.01.039. Epub 2014 Jan 30. PubMed PMID: 24486886. 5: Zhou S. Theoretical studies on binding and specificity mechanisms of farnesyltransferase (FTase) and geranylgeranyltransferase type-I (GGTase-I) inhibitors by molecular modeling. Comb Chem High Throughput Screen. 2014;17(6):509-19. PubMed PMID: 24444014. 6: Afshordel S, Wood WG, Igbavboa U, Muller WE, Eckert GP. Impaired geranylgeranyltransferase-I regulation reduces membrane-associated Rho protein levels in aged mouse brain. J Neurochem. 2014 May;129(4):732-42. doi: 10.1111/jnc.12654. Epub 2014 Feb 7. PubMed PMID: 24428713; PubMed Central PMCID: PMC3999261. 7: Cheng WH, Ho WY, Chang CF, Lu PJ, Cheng PW, Yeh TC, Hong LZ, Sun GC, Hsiao M, Tseng CJ. Simvastatin induces a central hypotensive effect via Ras-mediated signalling to cause eNOS up-regulation. Br J Pharmacol. 2013 Oct;170(4):847-58. doi: 10.1111/bph.12317. PubMed PMID: 23889671; PubMed Central PMCID: PMC3799598. 8: Merza M, Wetterholm E, Zhang S, Regner S, Thorlacius H. Inhibition of geranylgeranyltransferase attenuates neutrophil accumulation and tissue injury in severe acute pancreatitis. J Leukoc Biol. 2013 Sep;94(3):493-502. doi: 10.1189/jlb.1112546. Epub 2013 Jun 6. PubMed PMID: 23744643. 9: Al-haidari AA, Syk I, Jirström K, Thorlacius H. CCR4 mediates CCL17 (TARC)-induced migration of human colon cancer cells via RhoA/Rho-kinase signaling. Int J Colorectal Dis. 2013 Nov;28(11):1479-87. doi: 10.1007/s00384-013-1712-y. Epub 2013 May 7. PubMed PMID: 23649168. 10: Rehni AK, Singh TG. Pharmacological modulation of geranylgeranyltransferase and farnesyltransferase attenuates opioid withdrawal in vivo and in vitro. Neuropharmacology. 2013 Aug;71:19-26. doi: 10.1016/j.neuropharm.2013.01.022. Epub 2013 Feb 13. PubMed PMID: 23415632. 11: Zhang S, Rahman M, Jeppsson B, Herwald H, Thorlacius H. Geranylgeranyl transferase regulates streptococcal M1 protein-induced CXC chemokine formation and neutrophil recruitment in the lung. Shock. 2013 Mar;39(3):293-8. doi: 10.1097/SHK.0b013e3182844523. PubMed PMID: 23364431. 12: Clapp KM, Ellsworth ML, Sprague RS, Stephenson AH. Simvastatin and GGTI-2133, a geranylgeranyl transferase inhibitor, increase erythrocyte deformability but reduce low O(2) tension-induced ATP release. Am J Physiol Heart Circ Physiol. 2013 Mar 1;304(5):H660-6. doi: 10.1152/ajpheart.00635.2012. Epub 2013 Jan 18. PubMed PMID: 23335799; PubMed Central PMCID: PMC3602752. 13: Hasan Z, Rahman M, Palani K, Syk I, Jeppsson B, Thorlacius H. Geranylgeranyl transferase regulates CXC chemokine formation in alveolar macrophages and neutrophil recruitment in septic lung injury. Am J Physiol Lung Cell Mol Physiol. 2013 Feb 15;304(4):L221-9. doi: 10.1152/ajplung.00199.2012. Epub 2012 Dec 14. PubMed PMID: 23241528. 14: Griffiths GS, Grundl M, Allen JS 3rd, Matter ML. R-Ras interacts with filamin a to maintain endothelial barrier function. J Cell Physiol. 2011 Sep;226(9):2287-96. doi: 10.1002/jcp.22565. PubMed PMID: 21660952; PubMed Central PMCID: PMC3080452. 15: Cazzola M, Calzetta L, Page CP, Rinaldi B, Capuano A, Matera MG. Protein prenylation contributes to the effects of LPS on EFS-induced responses in human isolated bronchi. Am J Respir Cell Mol Biol. 2011 Oct;45(4):704-10. doi: 10.1165/rcmb.2010-0306OC. Epub 2011 Jan 28. PubMed PMID: 21278325. 16: Chiba Y, Sato S, Misawa M. GGTI-2133, an inhibitor of geranylgeranyltransferase, inhibits infiltration of inflammatory cells into airways in mouse experimental asthma. Int J Immunopathol Pharmacol. 2009 Oct-Dec;22(4):929-35. PubMed PMID: 20074456. 17: Chiba Y, Sato S, Hanazaki M, Sakai H, Misawa M. Inhibition of geranylgeranyltransferase inhibits bronchial smooth muscle hyperresponsiveness in mice. Am J Physiol Lung Cell Mol Physiol. 2009 Nov;297(5):L984-91. doi: 10.1152/ajplung.00178.2009. Epub 2009 Aug 28. PubMed PMID: 19717551. 18: Ohsawa M, Mutoh J, Hisa H. Mevalonate sensitizes the nociceptive transmission in the mouse spinal cord. Pain. 2008 Feb;134(3):285-92. Epub 2007 Aug 30. PubMed PMID: 17764839. 19: Johnson TE, Zhang X, Bleicher KB, Dysart G, Loughlin AF, Schaefer WH, Umbenhauer DR. Statins induce apoptosis in rat and human myotube cultures by inhibiting protein geranylgeranylation but not ubiquinone. Toxicol Appl Pharmacol. 2004 Nov 1;200(3):237-50. PubMed PMID: 15504460.