CaCCinh-A01
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Hodoodo CAT#: H555104

CAS#: 407587-33-1

Description: CaCCinh-A01, also known as TMEM16 Blocker I, is a TMEM16 Blocker. CaCCinh-A01 is a non-selective inhibitor of calcium-activated chloride channels (CaCCs) that blocks ATP-stimulated chloride conductance in human salivary gland, intestinal, and bronchial epithelium (mean IC50 = 10 µM).


Chemical Structure

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CaCCinh-A01
CAS# 407587-33-1

Theoretical Analysis

Hodoodo Cat#: H555104
Name: CaCCinh-A01
CAS#: 407587-33-1
Chemical Formula: C18H21NO4S
Exact Mass: 347.12
Molecular Weight: 347.429
Elemental Analysis: C, 62.23; H, 6.09; N, 4.03; O, 18.42; S, 9.23

Price and Availability

Size Price Availability Quantity
10mg USD 90 Ready to ship
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 450 Ready to ship
200mg USD 750 Ready to ship
500mg USD 1650 Ready to ship
1g USD 2650 2 Weeks
2g USD 4650 2 Weeks
Bulk inquiry

Synonym: CaCCinh-A01; CaCC(inh)-A01, TMEM16 Blocker I.

IUPAC/Chemical Name: 6-(1,1-dimethylethyl)-2-[(2-furanylcarbonyl)amino]-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid

InChi Key: ACLUEOBQFRYTQS-UHFFFAOYSA-N

InChi Code: InChI=1S/C18H21NO4S/c1-18(2,3)10-6-7-11-13(9-10)24-16(14(11)17(21)22)19-15(20)12-5-4-8-23-12/h4-5,8,10H,6-7,9H2,1-3H3,(H,19,20)(H,21,22)

SMILES Code: O=C(C1=C(NC(C2=CC=CO2)=O)SC3=C1CCC(C(C)(C)C)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:

Biological target: CaCCinh-A01 is an inhibitor of both TMEM16A and calcium-activated chloride channel (CaCC) with IC50s of 2.1 and 10 μM, respectively.
In vitro activity: It was found that CaCCinh-A01 reduces ANO1 protein levels by facilitating endoplasmic reticulum-associated, proteasomal turnover of ANO1. Washout of CaCCinh-A01 rescued ANO1 protein levels and resumed cell proliferation. Proliferation of newly derived CaCCinh-A01-resistant cell pools was not affected by CaCCinh-A01 as compared with the parental cells. Consistently, CaCCinh-A01 failed to reduce ANO1 protein levels in these cells, whereas ANO1 currents were still inhibited by CaCCinh-A01, indicating that CaCCinh-A01 inhibits cell proliferation by reducing ANO1 protein levels. Reference: J Biol Chem. 2014 Apr 18;289(16):11029-11041. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24599954/
In vivo activity: To determine the effect of TMEM16A inhibitors after ischemic stroke, the infarct size of mouse brains was measured by TTC at different time points. The results showed that Caccinh-A01 significantly reduced infarction: 29.50 (22.63–31.88) with MCAO-saline treatment vs. 17.25 (15.38–22.63) with MCAO-Caccinh-A01 treatment at 24 h (p < 0.05); 27.75 (23.63–32.25) with MCAO-saline treatment vs. 15.75 (12.13–21.23) with MCAO-Caccinh-A01 treatment at 72 h (p < 0.05; n = 6/group) (Figures 2A,B). Neurological severity scores, the grip strength test and rotarod test were applied to test motor function, sensorimotor coordination,and muscular strength on each mouse after ischemic injury. As shown in Figures 2C–E, mice treated with Caccinh-A01 manifested better behavioral performance at 24 and 72 h than mice in the saline group (NSS: 10.50 (9.25–11.00) with MCAO-saline treatment vs. 6.50 (5.75–10.00) with MCAO-Caccinh-A01 treatment at 24 h, p < 0.01; 9.50 (7.75–10.00) with MCAO-saline treatment vs. 5.00 (3.75–6.00) with MCAO-Caccinh-A01 treatment at 72 h, p < 0.01. Grip strength test: 55.50 (24.00–79.25) with MCAO-saline treatment vs. 81.50 (69.25–90.00) with MCAO-Caccinh-A01 treatment at 24 h, p < 0.05; 61.50 (53.00–86.75) with MCAO-saline treatment vs. 94.00 (81.00–106.25) with MCAO-Caccinh-A01 treatment at 72 h, p < 0.05. Rotarod test: 47.50 (20.75–80.25) with MCAO-saline treatment vs. 115.00 (74.75–196.25) with MCAO-Caccinh-A01 treatment at 24 h, p < 0.01; 64.00 (46.50–104.00) with MCAO-saline treatment vs. 137.00 (96.75–232.50) with MCAO-Caccinh-A01 treatment at 72 h, p < 0.01. n = 10/group). Reference: Front Cell Neurosci. 2019 Aug 6;13:360. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31447648/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 69.0 198.60

Preparing Stock Solutions

The following data is based on the product molecular weight 347.43 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.

Recalculate based on batch purity %
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:
In vitro protocol: 1. Bill A, Hall ML, Borawski J, Hodgson C, Jenkins J, Piechon P, Popa O, Rothwell C, Tranter P, Tria S, Wagner T, Whitehead L, Gaither LA. Small molecule-facilitated degradation of ANO1 protein: a new targeting approach for anticancer therapeutics. J Biol Chem. 2014 Apr 18;289(16):11029-11041. doi: 10.1074/jbc.M114.549188. Epub 2014 Mar 5. PMID: 24599954; PMCID: PMC4036244. 2. Namkung W, Phuan PW, Verkman AS. TMEM16A inhibitors reveal TMEM16A as a minor component of calcium-activated chloride channel conductance in airway and intestinal epithelial cells. J Biol Chem. 2011 Jan 21;286(3):2365-74. doi: 10.1074/jbc.M110.175109. Epub 2010 Nov 17. PMID: 21084298; PMCID: PMC3023530.
In vivo protocol: 1. Liu PY, Zhang Z, Liu Y, Tang XL, Shu S, Bao XY, Zhang Y, Gu Y, Xu Y, Cao X. TMEM16A Inhibition Preserves Blood-Brain Barrier Integrity After Ischemic Stroke. Front Cell Neurosci. 2019 Aug 6;13:360. doi: 10.3389/fncel.2019.00360. PMID: 31447648; PMCID: PMC6691060.

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1: Hannigan KI, Griffin CS, Large RJ, Sergeant GP, Hollywood MA, McHale NG, Thornbury KD. The role of Ca(2+)-activated Cl(-) current in tone generation in the rabbit corpus cavernosum. Am J Physiol Cell Physiol. 2017 Nov 1;313(5):C475-C486. doi: 10.1152/ajpcell.00025.2017. Epub 2017 Aug 23. PubMed PMID: 28835432.

2: Fedigan S, Bradley E, Webb T, Large RJ, Hollywood MA, Thornbury KD, McHale NG, Sergeant GP. Effects of new-generation TMEM16A inhibitors on calcium-activated chloride currents in rabbit urethral interstitial cells of Cajal. Pflugers Arch. 2017 Jul 21. doi: 10.1007/s00424-017-2028-5. [Epub ahead of print] PubMed PMID: 28733893.

3: Banerjee J, Leung CT, Li A, Peterson-Yantorno K, Ouyang H, Stamer WD, Civan MM. Regulatory Roles of Anoctamin-6 in Human Trabecular Meshwork Cells. Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):492-501. doi: 10.1167/iovs.16-20188. PubMed PMID: 28125837; PubMed Central PMCID: PMC5283088.

4: Yu B, Jiang Y, Jin L, Ma T, Yang H. Role of Quercetin in Modulating Chloride Transport in the Intestine. Front Physiol. 2016 Nov 23;7:549. eCollection 2016. PubMed PMID: 27932986; PubMed Central PMCID: PMC5120089.

5: Guan L, Song Y, Gao J, Gao J, Wang K. Inhibition of calcium-activated chloride channel ANO1 suppresses proliferation and induces apoptosis of epithelium originated cancer cells. Oncotarget. 2016 Nov 29;7(48):78619-78630. doi: 10.18632/oncotarget.12524. PubMed PMID: 27732935; PubMed Central PMCID: PMC5346664.

6: Kamikawa A, Ichii O, Sakazaki J, Ishikawa T. Ca2+-activated Cl- channel currents in mammary secretory cells from lactating mouse. Am J Physiol Cell Physiol. 2016 Nov 1;311(5):C808-C819. doi: 10.1152/ajpcell.00050.2016. Epub 2016 Aug 24. PubMed PMID: 27558156.

7: Gianotti A, Ferrera L, Philp AR, Caci E, Zegarra-Moran O, Galietta LJ, Flores CA. Pharmacological analysis of epithelial chloride secretion mechanisms in adult murine airways. Eur J Pharmacol. 2016 Jun 15;781:100-8. doi: 10.1016/j.ejphar.2016.04.007. Epub 2016 Apr 7. PubMed PMID: 27063443.

8: Hwang SJ, Basma N, Sanders KM, Ward SM. Effects of new-generation inhibitors of the calcium-activated chloride channel anoctamin 1 on slow waves in the gastrointestinal tract. Br J Pharmacol. 2016 Apr;173(8):1339-49. doi: 10.1111/bph.13431. Epub 2016 Mar 6. PubMed PMID: 26774021; PubMed Central PMCID: PMC4940814.

9: Chatterjee T, Sheikh IA, Chakravarty D, Chakrabarti P, Sarkar P, Saha T, Chakrabarti MK, Hoque KM. Effects of Small Molecule Calcium-Activated Chloride Channel Inhibitors on Structure and Function of Accessory Cholera Enterotoxin (Ace) of Vibrio cholerae. PLoS One. 2015 Nov 5;10(11):e0141283. doi: 10.1371/journal.pone.0141283. eCollection 2015. PubMed PMID: 26540279; PubMed Central PMCID: PMC4634967.

10: Cherkashin AP, Kolesnikova AS, Tarasov MV, Romanov RA, Rogachevskaja OA, Bystrova MF, Kolesnikov SS. Expression of calcium-activated chloride channels Ano1 and Ano2 in mouse taste cells. Pflugers Arch. 2016 Feb;468(2):305-19. doi: 10.1007/s00424-015-1751-z. Epub 2015 Nov 3. PubMed PMID: 26530828.

11: Pineda-Farias JB, Barragán-Iglesias P, Loeza-Alcocer E, Torres-López JE, Rocha-González HI, Pérez-Severiano F, Delgado-Lezama R, Granados-Soto V. Role of anoctamin-1 and bestrophin-1 in spinal nerve ligation-induced neuropathic pain in rats. Mol Pain. 2015 Jul 1;11:41. doi: 10.1186/s12990-015-0042-1. PubMed PMID: 26130088; PubMed Central PMCID: PMC4487556.

12: Boedtkjer DM, Kim S, Jensen AB, Matchkov VM, Andersson KE. New selective inhibitors of calcium-activated chloride channels - T16A(inh) -A01, CaCC(inh) -A01 and MONNA - what do they inhibit? Br J Pharmacol. 2015 Aug;172(16):4158-72. doi: 10.1111/bph.13201. Epub 2015 Jul 8. PubMed PMID: 26013995; PubMed Central PMCID: PMC4543620.

13: Sanders KM, O'Driscoll K, Leblanc N. Pharmacological properties of native CaCCs and TMEM16A. Channels (Austin). 2014;8(6):473-4. doi: 10.4161/19336950.2014.986624. PubMed PMID: 25528999; PubMed Central PMCID: PMC4594607.

14: Sauter DRP, Novak I, Pedersen SF, Larsen EH, Hoffmann EK. ANO1 (TMEM16A) in pancreatic ductal adenocarcinoma (PDAC). Pflugers Arch. 2015 Jul;467(7):1495-1508. doi: 10.1007/s00424-014-1598-8. Epub 2014 Aug 28. PubMed PMID: 25163766; PubMed Central PMCID: PMC4464647.

15: Liu Y, Zhang H, Huang D, Qi J, Xu J, Gao H, Du X, Gamper N, Zhang H. Characterization of the effects of Cl⁻ channel modulators on TMEM16A and bestrophin-1 Ca²⁺ activated Cl⁻ channels. Pflugers Arch. 2015 Jul;467(7):1417-1430. doi: 10.1007/s00424-014-1572-5. Epub 2014 Aug 1. PubMed PMID: 25078708.

16: García G, Martínez-Rojas VA, Rocha-González HI, Granados-Soto V, Murbartián J. Evidence for the participation of Ca(2+)-activated chloride channels in formalin-induced acute and chronic nociception. Brain Res. 2014 Sep 4;1579:35-44. doi: 10.1016/j.brainres.2014.07.011. Epub 2014 Jul 15. PubMed PMID: 25036442.

17: Bill A, Hall ML, Borawski J, Hodgson C, Jenkins J, Piechon P, Popa O, Rothwell C, Tranter P, Tria S, Wagner T, Whitehead L, Gaither LA. Small molecule-facilitated degradation of ANO1 protein: a new targeting approach for anticancer therapeutics. J Biol Chem. 2014 Apr 18;289(16):11029-41. doi: 10.1074/jbc.M114.549188. Epub 2014 Mar 5. PubMed PMID: 24599954; PubMed Central PMCID: PMC4036244.

18: Qi J, Wang Y, Liu Y, Zhang F, Guan B, Zhang H. Development and validation of HTS assay for screening the calcium-activated chloride channel modulators in TMEM16A stably expressed CHO cells. Anal Bioanal Chem. 2014 Feb;406(6):1713-21. doi: 10.1007/s00216-013-7550-5. Epub 2014 Jan 22. PubMed PMID: 24448969.

19: Ko EA, Jin BJ, Namkung W, Ma T, Thiagarajah JR, Verkman AS. Chloride channel inhibition by a red wine extract and a synthetic small molecule prevents rotaviral secretory diarrhoea in neonatal mice. Gut. 2014 Jul;63(7):1120-9. doi: 10.1136/gutjnl-2013-305663. Epub 2013 Sep 19. PubMed PMID: 24052273; PubMed Central PMCID: PMC4048772.

20: Ousingsawat J, Kongsuphol P, Schreiber R, Kunzelmann K. CFTR and TMEM16A are separate but functionally related Cl- channels. Cell Physiol Biochem. 2011;28(4):715-24. doi: 10.1159/000335765. Epub 2011 Dec 14. PubMed PMID: 22178883.