GW 441756 | GW441756 | CAS#504433-23-2 | TrkA inhibitor

GW-441756
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406799

CAS#: 504433-23-2

Description: GW-441756 is a potent inhibitor of TrkA (IC50 = 2 nM). Trk inhibition reduces cell proliferation and potentiates the effects of chemotherapeutic agents in Ewing sarcoma.

Chemical Structure

GW-441756

CAS# 504433-23-2

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406799
Name: GW-441756
CAS#: 504433-23-2
Chemical Formula: C17H13N3O
Exact Mass: 275.11
Molecular Weight: 275.311
Elemental Analysis: C, 74.17; H, 4.76; N, 15.26; O, 5.81

Price and Availability

Size	Price	Availability
25mg	USD 250	2 Weeks
50mg	USD 450	2 Weeks
100mg	USD 750	2 Weeks
200mg	USD 1250	2 Weeks
500mg	USD 2650	2 Weeks
1g	USD 3850	2 Weeks
2g	USD 6450	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: GW-441756; GW 441756; GW441756.

IUPAC/Chemical Name: 1,3-dihydro-3-[(1-methyl-1H-indol-3-yl)methylene]-2H-pyrrolo[3,2-b]pyridin-2-one

InChi Key: NXNQLECPAXXYTR-LCYFTJDESA-N

InChi Code: InChI=1S/C17H13N3O/c1-20-10-11(12-5-2-3-7-15(12)20)9-13-16-14(19-17(13)21)6-4-8-18-16/h2-10H,1H3,(H,19,21)/b13-9-

SMILES Code: O=C1/C(C2=NC=CC=C2N1)=C\C3=CN(C)C4=C3C=CC=C4

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:	GW 441756 is a potent and specific nerve growth factor (NGF) receptor tyrosine kinases A (TrkA) inhibitor (IC50=2 nM), which eliminates the BmK NSPK-induced neurite outgrowth.
In vitro activity:	GW441756 significantly (p < 0.05 in Figures 3A,B and Supplementary Figure 2F) reduced the NGF effect, leaving almost unaltered the spheroid size when used alone, as a control. Reference: Front Cell Dev Biol. 2021 Jun 29;9:676568. https://pubmed.ncbi.nlm.nih.gov/34268306/
In vivo activity:	The mechanical pain threshold of WAS group decrease from day 0 basal value of 40 ± 24 g to day 10 value of 6 ± 2 g (Fig. 2E; paired t test: p = 0.0415). The daily administration of GW441756 prevented the decrease in mechanical pain threshold. At day 0 the rats presented abdominal mechanical pain threshold of 37 ± 19 g and at day 10 the mechanical pain threshold was 25 ± 18 g (Fig. 2F; paired t test: p = 0.2374). Reference: Sci Rep. 2019 Oct 1;9(1):14113. https://pubmed.ncbi.nlm.nih.gov/31575913/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	13.5	49.15

Preparing Stock Solutions

The following data is based on the product molecular weight 275.31 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. Di Donato M, Galasso G, Giovannelli P, Sinisi AA, Migliaccio A, Castoria G. Targeting the Nerve Growth Factor Signaling Impairs the Proliferative and Migratory Phenotype of Triple-Negative Breast Cancer Cells. Front Cell Dev Biol. 2021 Jun 29;9:676568. doi: 10.3389/fcell.2021.676568. PMID: 34268306; PMCID: PMC8275826. 2. Ruggeri P, Farina AR, Di Ianni N, Cappabianca L, Ragone M, Ianni G, Gulino A, Mackay AR. The TrkAIII oncoprotein inhibits mitochondrial free radical ROS-induced death of SH-SY5Y neuroblastoma cells by augmenting SOD2 expression and activity at the mitochondria, within the context of a tumour stem cell-like phenotype. PLoS One. 2014 Apr 15;9(4):e94568. doi: 10.1371/journal.pone.0094568. PMID: 24736663; PMCID: PMC3988074. 3. Dias B, Serrão P, Cruz F, Charrua A. Effect of Water Avoidance Stress on serum and urinary NGF levels in rats: diagnostic and therapeutic implications for BPS/IC patients. Sci Rep. 2019 Oct 1;9(1):14113. doi: 10.1038/s41598-019-50576-4. PMID: 31575913; PMCID: PMC6773881. 4. Zhang Q, Descamps O, Hart MJ, Poksay KS, Spilman P, Kane DJ, Gorostiza O, John V, Bredesen DE. Paradoxical effect of TrkA inhibition in Alzheimer's disease models. J Alzheimers Dis. 2014;40(3):605-617. doi: 10.3233/JAD-130017. PMID: 24531152; PMCID: PMC4091737.
In vitro protocol:	1. Di Donato M, Galasso G, Giovannelli P, Sinisi AA, Migliaccio A, Castoria G. Targeting the Nerve Growth Factor Signaling Impairs the Proliferative and Migratory Phenotype of Triple-Negative Breast Cancer Cells. Front Cell Dev Biol. 2021 Jun 29;9:676568. doi: 10.3389/fcell.2021.676568. PMID: 34268306; PMCID: PMC8275826. 2. Ruggeri P, Farina AR, Di Ianni N, Cappabianca L, Ragone M, Ianni G, Gulino A, Mackay AR. The TrkAIII oncoprotein inhibits mitochondrial free radical ROS-induced death of SH-SY5Y neuroblastoma cells by augmenting SOD2 expression and activity at the mitochondria, within the context of a tumour stem cell-like phenotype. PLoS One. 2014 Apr 15;9(4):e94568. doi: 10.1371/journal.pone.0094568. PMID: 24736663; PMCID: PMC3988074.
In vivo protocol:	1. Dias B, Serrão P, Cruz F, Charrua A. Effect of Water Avoidance Stress on serum and urinary NGF levels in rats: diagnostic and therapeutic implications for BPS/IC patients. Sci Rep. 2019 Oct 1;9(1):14113. doi: 10.1038/s41598-019-50576-4. PMID: 31575913; PMCID: PMC6773881. 2. Zhang Q, Descamps O, Hart MJ, Poksay KS, Spilman P, Kane DJ, Gorostiza O, John V, Bredesen DE. Paradoxical effect of TrkA inhibition in Alzheimer's disease models. J Alzheimers Dis. 2014;40(3):605-617. doi: 10.3233/JAD-130017. PMID: 24531152; PMCID: PMC4091737.

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1: Kudo TA, Kanetaka H, Mochizuki K, Tominami K, Nunome S, Abe G, Kosukegawa H, Abe T, Mori H, Mori K, Takagi T, Izumi S. Induction of neurite outgrowth in PC12 cells treated with temperature-controlled repeated thermal stimulation. PLoS One. 2015 Apr 16;10(4):e0124024. doi: 10.1371/journal.pone.0124024. eCollection 2015. PubMed PMID: 25879210; PubMed Central PMCID: PMC4399938.

2: Bernard-Gauthier V, Aliaga A, Aliaga A, Boudjemeline M, Hopewell R, Kostikov A, Rosa-Neto P, Thiel A, Schirrmacher R. Syntheses and evaluation of carbon-11- and fluorine-18-radiolabeled pan-tropomyosin receptor kinase (Trk) inhibitors: exploration of the 4-aza-2-oxindole scaffold as Trk PET imaging agents. ACS Chem Neurosci. 2015 Feb 18;6(2):260-76. doi: 10.1021/cn500193f. Epub 2014 Nov 10. PubMed PMID: 25350780.

3: Ruggeri P, Farina AR, Di Ianni N, Cappabianca L, Ragone M, Ianni G, Gulino A, Mackay AR. The TrkAIII oncoprotein inhibits mitochondrial free radical ROS-induced death of SH-SY5Y neuroblastoma cells by augmenting SOD2 expression and activity at the mitochondria, within the context of a tumour stem cell-like phenotype. PLoS One. 2014 Apr 15;9(4):e94568. doi: 10.1371/journal.pone.0094568. eCollection 2014. PubMed PMID: 24736663; PubMed Central PMCID: PMC3988074.

4: Zhang Q, Descamps O, Hart MJ, Poksay KS, Spilman P, Kane DJ, Gorostiza O, John V, Bredesen DE. Paradoxical effect of TrkA inhibition in Alzheimer's disease models. J Alzheimers Dis. 2014;40(3):605-17. doi: 10.3233/JAD-130017. PubMed PMID: 24531152; PubMed Central PMCID: PMC4091737.

5: Jung EJ, Lee SY, Kim CW. Proteomic analysis of novel targets associated with TrkA-mediated tyrosine phosphorylation signaling pathways in SK-N-MC neuroblastoma cells. Proteomics. 2013 Jan;13(2):355-67. doi: 10.1002/pmic.201200251. PubMed PMID: 23319303; PubMed Central PMCID: PMC3580882.

6: Hermanson SB, Carlson CB, Riddle SM, Zhao J, Vogel KW, Nichols RJ, Bi K. Screening for novel LRRK2 inhibitors using a high-throughput TR-FRET cellular assay for LRRK2 Ser935 phosphorylation. PLoS One. 2012;7(8):e43580. doi: 10.1371/journal.pone.0043580. Epub 2012 Aug 28. PubMed PMID: 22952710; PubMed Central PMCID: PMC3429506.

7: Vera C, Tapia V, Kohan K, Gabler F, Ferreira A, Selman A, Vega M, Romero C. Nerve growth factor induces the expression of chaperone protein calreticulin in human epithelial ovarian cells. Horm Metab Res. 2012 Jul;44(8):639-43. doi: 10.1055/s-0032-1311633. Epub 2012 Jul 6. PubMed PMID: 22773372.

8: Kudo TA, Kanetaka H, Mizuno K, Ryu Y, Miyamoto Y, Nunome S, Zhang Y, Kano M, Shimizu Y, Hayashi H. Dorsomorphin stimulates neurite outgrowth in PC12 cells via activation of a protein kinase A-dependent MEK-ERK1/2 signaling pathway. Genes Cells. 2011 Nov;16(11):1121-32. doi: 10.1111/j.1365-2443.2011.01556.x. Epub 2011 Oct 12. PubMed PMID: 21988724.

9: Jung EJ, Kim CW, Kim DR. Cytosolic accumulation of gammaH2AX is associated with tropomyosin-related kinase A-induced cell death in U2OS cells. Exp Mol Med. 2008 Jun 30;40(3):276-85. PubMed PMID: 18587265; PubMed Central PMCID: PMC2679291.

10: Jung EJ, Kim DR. Apoptotic cell death in TrkA-overexpressing cells: kinetic regulation of ERK phosphorylation and caspase-7 activation. Mol Cells. 2008 Jul 31;26(1):12-7. Epub 2008 May 20. PubMed PMID: 18511888.

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