GLPG-1837 | ABBV-974 | CAS#1654725-02-6 | CFTR Potentiator

GLPG1837
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 555122

CAS#: 1654725-02-6

Description: GLPG-1837, also known as ABBV-974, is a novel cystic fibrosis transmembrane conductance regulator (CFTR) potentiator1. GLPG1837 was generally safe and well tolerated in healthy subjects up to the highest dose of 800 mg twice daily for 2 weeks. GLPG1837 shows enhanced efficacy on CFTR mutants harboring Class III mutations compared to Ivacaftor, the first marketed potentiator.

Chemical Structure

GLPG1837

CAS# 1654725-02-6

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 555122
Name: GLPG1837
CAS#: 1654725-02-6
Chemical Formula: C16H20N4O3S
Exact Mass: 348.13
Molecular Weight: 348.420
Elemental Analysis: C, 55.16; H, 5.79; N, 16.08; O, 13.78; S, 9.20

Price and Availability

Size	Price	Availability
10mg	USD 150	Ready to ship
25mg	USD 250	Ready to ship
50mg	USD 450	Ready to ship
100mg	USD 750	Ready to ship
200mg	USD 1250	Ready to ship
500mg	USD 2750	Ready to ship
1g	USD 3850	Ready to ship
2g	USD 5650	Ready to ship
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: GLPG-1837; GLPG 1837; GLPG1837; ABBV-974; ABBV 974; ABBV974

IUPAC/Chemical Name: N-(3-carbamoyl-5,5,7,7-tetramethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-2-yl)-1H-pyrazole-3-carboxamide

InChi Key: GHTGYZMBQPXTCQ-UHFFFAOYSA-N

InChi Code: InChI=1S/C16H20N4O3S/c1-15(2)7-8-10(12(17)21)14(24-11(8)16(3,4)23-15)19-13(22)9-5-6-18-20-9/h5-6H,7H2,1-4H3,(H2,17,21)(H,18,20)(H,19,22)

SMILES Code: O=C(C1=NNC=C1)NC(S2)=C(C(N)=O)C3=C2C(C)(C)OC(C)(C)C3

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: Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR). With the discovery of Ivacaftor and Orkambi, it has been shown that CFTR function can be partially restored by administering one or more small molecules. These molecules aim at either enhancing the amount of CFTR on the cell surface (correctors) or at improving the gating function of the CFTR channel (potentiators).

Product Data:

Product Data

Certificate of Analysis:

View CoA: current batch, Lot#C8R11B21

QC Data:

View QC data: current batch, Lot#C8R11B21

Safety Data Sheet (SDS):

View Safety Data Sheet (SDS)

Instruction:

View handling instruction

Biological target:	GLPG1837 is a potent and reversible CFTR potentiator, with EC50s of 3 nM and 339 nM for F508del and G551D CFTR, respectively.
In vitro activity:	As a first step to characterize GLPG1837, this study examined the effect of acute addition of this compound to macroscopic WT-CFTR currents preactivated with PKA and ATP to a steady state at a holding potential of −30 mV in excised inside-out patches. Fig. 2 A shows a representative real-time recording in which an application of 3 µM GLPG1837 in the continuous presence of ATP enhances the currents by 2.06 ± 0.08-fold (n = 19). This potentiation effect is reversible and concentration dependent. The dose responses at different concentrations of GLPG1837 were normalized to the currents at 3 µM GLPG1837 in the same patch, and the data can be fitted with the Hill equation, yielding a K1/2 of 0.23 ± 0.12 µM and a Hill coefficient of 0.70 ± 0.24 (Fig. 2 B). Reference: J Gen Physiol. 2017 Dec 4; 149(12): 1105–1118. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715911/
In vivo activity:	TBD

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	159.5	457.78
	Ethanol	5.0	14.35

Preparing Stock Solutions

The following data is based on the product molecular weight 348.42 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. Yeh HI, Sohma Y, Conrath K, Hwang TC. A common mechanism for CFTR potentiators. J Gen Physiol. 2017 Dec 4;149(12):1105-1118. doi: 10.1085/jgp.201711886. Epub 2017 Oct 27. PMID: 29079713; PMCID: PMC5715911.
In vitro protocol:	1. Yeh HI, Sohma Y, Conrath K, Hwang TC. A common mechanism for CFTR potentiators. J Gen Physiol. 2017 Dec 4;149(12):1105-1118. doi: 10.1085/jgp.201711886. Epub 2017 Oct 27. PMID: 29079713; PMCID: PMC5715911.
In vivo protocol:	TBD

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1: Van der Plas SE, Kelgtermans H, De Munck T, Martina SLX, Dropsit S, Quinton E, De Blieck A, Joannesse C, Tomaskovic L, Jans M, Christophe T, van der Aar E, Borgonovi M, Nelles L, Gees M, Stouten P, Van Der Schueren J, Mammoliti O, Conrath K, Andrews M. Discovery of N-(3-Carbamoyl-5,5,7,7-tetramethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-2-yl)-lH-pyr azole-5-carboxamide (GLPG1837), a Novel Potentiator Which Can Open Class III Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channels to a High Extent. J Med Chem. 2018 Feb 22;61(4):1425-1435. doi: 10.1021/acs.jmedchem.7b01288. Epub 2018 Jan 10. PubMed PMID: 29148763.

2: DeStefano S, Gees M, Hwang TC. Physiological and pharmacological characterization of the N1303K mutant CFTR. J Cyst Fibros. 2018 Sep;17(5):573-581. doi: 10.1016/j.jcf.2018.05.011. Epub 2018 Jun 7. PubMed PMID: 29887518.

3: Gees M, Musch S, Van der Plas S, Wesse AS, Vandevelde A, Verdonck K, Mammoliti O, Hwang TC, Sonck K, Stouten P, Swensen AM, Jans M, Van der Schueren J, Nelles L, Andrews M, Conrath K. Identification and Characterization of Novel CFTR Potentiators. Front Pharmacol. 2018 Oct 26;9:1221. doi: 10.3389/fphar.2018.01221. eCollection 2018. PubMed PMID: 30416447; PubMed Central PMCID: PMC6212544.

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