CITCO | CAS#338404-52-7

MedKoo Cat#: 407340 | Name: CITCO

Description:

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

CITCO is a constitutive androstane receptor (CAR) agonist.

Chemical Structure

CITCO

CAS#338404-52-7

Theoretical Analysis

MedKoo Cat#: 407340

Name: CITCO

CAS#: 338404-52-7

Chemical Formula: C19H12Cl3N3OS

Exact Mass: 434.9767

Molecular Weight: 436.74

Elemental Analysis: C, 52.25; H, 2.77; Cl, 24.35; N, 9.62; O, 3.66; S, 7.34

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to Ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,450.00	Ready to ship
1g	USD 3,650.00	2 Weeks
2g	USD 5,850.00	2 Weeks

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Related CAS #

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Synonym

CITCO

IUPAC/Chemical Name

(E)-6-(4-chlorophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl) oxime

InChi Key

ZQWBOKJVVYNKTL-AUEPDCJTSA-N

InChi Code

InChI=1S/C19H12Cl3N3OS/c20-14-4-2-13(3-5-14)18-17(25-7-8-27-19(25)24-18)10-23-26-11-12-1-6-15(21)16(22)9-12/h1-10H,11H2/b23-10+

SMILES Code

ClC1=CC=C(C=C1Cl)CO/N=C/C2=C(C3=CC=C(Cl)C=C3)N=C4SC=CN42

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, not in water

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

Moreover, the beneficial effects of CITCO were abrogated when CAR knockout HepaRG cells were used in the coculture model. Importantly, synergistic anticancer effects were observed between CITCO and CHOP, in that inclusion of CITCO alongside the CHOP regimen offers comparable antineoplastic activity toward lymphoma cells at significantly reduced drug concentrations, and the decreased CHOP load attenuates cardiotoxicity. Overall, these findings provide a potentially promising novel strategy for facilitating CHOP-based chemotherapy. Mol Cancer Ther; 15(3); 392-401. ©2016 AACR.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A23T06K27

QC Data

View QC data: current batch, Lot#A23T06K27

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

CITCO is a potent CAR agonist (EC50 = 49 nM). CITCO altered expression of key drug-metabolizing enzymes and transporters in human hepatocytes, which positively affects the metabolic profile of CHOP. Coadministration of CITCO and CHOP in the coculture model led to significantly enhanced cytotoxicity in lymphoma cells but not in cardiomyocytes. CAR-driven regeneration protects liver from failure following tissue loss. The constitutive androstane receptor (CAR and NR1i3) is a key regulator of CYP2B6.

In vitro activity:

This study showed that CITCO: 1) binds directly to hPXR; 2) activates hPXR in HepG2 cells, with activation being blocked by an hPXR-specific antagonist, SPA70; 3) does not activate mouse PXR; 4) depends on tryptophan-299 to activate hPXR; 5) recruits steroid receptor coactivator 1 to hPXR; 6) activates hPXR in HepaRG cell lines even when hCAR is knocked out; and 7) activates hPXR in primary human hepatocytes. Reference: Mol Pharmacol. 2020 Mar;97(3):180-190. https://pubmed.ncbi.nlm.nih.gov/31882411/

In vivo activity:

This in vivo study determined CITCO as an effective facilitator for cyclophosphamide-based non-Hodgkin's lymphoma treatment with a pharmacokinetic profile favoring oral administration, promoting CITCO as a promising adjuvant candidate for cyclophosphamide-based regimens. Reference: Cells. 2020 Nov 21;9(11):2520. https://pubmed.ncbi.nlm.nih.gov/33233444/

	Solvent	mg/mL	mM
Solubility
	DMSO	21.8	50.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 436.74 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. Lin W, Bwayi M, Wu J, Li Y, Chai SC, Huber AD, Chen T. CITCO Directly Binds to and Activates Human Pregnane X Receptor. Mol Pharmacol. 2020 Mar;97(3):180-190. doi: 10.1124/mol.119.118513. Epub 2019 Dec 27. PMID: 31882411; PMCID: PMC6978709. 2. Lemmen J, Tozakidis IE, Bele P, Galla HJ. Constitutive androstane receptor upregulates Abcb1 and Abcg2 at the blood-brain barrier after CITCO activation. Brain Res. 2013 Mar 21;1501:68-80. doi: 10.1016/j.brainres.2013.01.025. Epub 2013 Jan 20. PMID: 23340159. 3. Kurian R, Hedrich W, Mackowiak B, Li L, Wang H. CITCO as an Adjuvant Facilitates CHOP-Based Lymphoma Treatment in hCAR-Transgenic Mice. Cells. 2020 Nov 21;9(11):2520. doi: 10.3390/cells9112520. PMID: 33233444; PMCID: PMC7700167. 4. Chakraborty S, Kanakasabai S, Bright JJ. Constitutive androstane receptor agonist CITCO inhibits growth and expansion of brain tumour stem cells. Br J Cancer. 2011 Feb 1;104(3):448-59. doi: 10.1038/sj.bjc.6606064. Epub 2011 Jan 11. PMID: 21224854; PMCID: PMC3049563.

In vitro protocol:

In vivo protocol:

1. Kurian R, Hedrich W, Mackowiak B, Li L, Wang H. CITCO as an Adjuvant Facilitates CHOP-Based Lymphoma Treatment in hCAR-Transgenic Mice. Cells. 2020 Nov 21;9(11):2520. doi: 10.3390/cells9112520. PMID: 33233444; PMCID: PMC7700167. 2. Chakraborty S, Kanakasabai S, Bright JJ. Constitutive androstane receptor agonist CITCO inhibits growth and expansion of brain tumour stem cells. Br J Cancer. 2011 Feb 1;104(3):448-59. doi: 10.1038/sj.bjc.6606064. Epub 2011 Jan 11. PMID: 21224854; PMCID: PMC3049563.

1: Smutný T, Nova A, Drechslerová M, Fernandez AC, Hyrsova L, Hrušková ZR, Kunes J, Pour M, Spulák M, Pavek P. 2-(3-Methoxyphenyl)quinazoline Derivatives: A New Class of Direct Constitutive Androstane Receptor (CAR) Agonists. J Med Chem. 2016 May 4. [Epub ahead of print] PubMed PMID: 27145071. 2: Kandel BA, Thomas M, Winter S, Damm G, Seehofer D, Burk O, Schwab M, Zanger UM. Genomewide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR and PPARα in primary human hepatocytes. Biochim Biophys Acta. 2016 Mar 17. pii: S1874-9399(16)30046-3. doi: 10.1016/j.bbagrm.2016.03.007. [Epub ahead of print] PubMed PMID: 26994748. 3: Tschuor C, Kachaylo E, Limani P, Raptis DA, Linecker M, Tian Y, Herrmann U, Grabliauskaite K, Weber A, Columbano A, Graf R, Humar B, Clavien PA. Constitutive androstane receptor (Car)-driven regeneration protects liver from failure following tissue loss. J Hepatol. 2016 Mar 3. pii: S0168-8278(16)30006-X. doi: 10.1016/j.jhep.2016.02.040. [Epub ahead of print] PubMed PMID: 26948495. 4: Hedrich WD, Xiao J, Heyward S, Zhang Y, Zhang J, Baer MR, Hassan HE, Wang H. Activation of the Constitutive Androstane Receptor Increases the Therapeutic Index of CHOP in Lymphoma Treatment. Mol Cancer Ther. 2016 Mar;15(3):392-401. doi: 10.1158/1535-7163.MCT-15-0667. Epub 2016 Jan 28. PubMed PMID: 26823489; PubMed Central PMCID: PMC4783244. 5: Rondini EA, Duniec-Dmuchowski Z, Kocarek TA. Nonsterol Isoprenoids Activate Human Constitutive Androstane Receptor in an Isoform-Selective Manner in Primary Cultured Mouse Hepatocytes. Drug Metab Dispos. 2016 Apr;44(4):595-604. doi: 10.1124/dmd.115.068551. Epub 2016 Jan 21. PubMed PMID: 26798158; PubMed Central PMCID: PMC4810768. 6: Li D, Mackowiak B, Brayman TG, Mitchell M, Zhang L, Huang SM, Wang H. Genome-wide analysis of human constitutive androstane receptor (CAR) transcriptome in wild-type and CAR-knockout HepaRG cells. Biochem Pharmacol. 2015 Nov 1;98(1):190-202. doi: 10.1016/j.bcp.2015.08.087. Epub 2015 Aug 12. PubMed PMID: 26275810; PubMed Central PMCID: PMC4600658. 7: Oshida K, Vasani N, Jones C, Moore T, Hester S, Nesnow S, Auerbach S, Geter DR, Aleksunes LM, Thomas RS, Applegate D, Klaassen CD, Corton JC. Identification of chemical modulators of the constitutive activated receptor (CAR) in a gene expression compendium. Nucl Recept Signal. 2015 Apr 27;13:e002. doi: 10.1621/nrs.13002. eCollection 2015. PubMed PMID: 25949234; PubMed Central PMCID: PMC4422105. 8: Carazo A, Pávek P. The Use of the LanthaScreen TR-FRET CAR Coactivator Assay in the Characterization of Constitutive Androstane Receptor (CAR) Inverse Agonists. Sensors (Basel). 2015 Apr 21;15(4):9265-76. doi: 10.3390/s150409265. PubMed PMID: 25905697; PubMed Central PMCID: PMC4431184. 9: Thomas M, Bayha C, Vetter S, Hofmann U, Schwarz M, Zanger UM, Braeuning A. Activating and Inhibitory Functions of WNT/β-Catenin in the Induction of Cytochromes P450 by Nuclear Receptors in HepaRG Cells. Mol Pharmacol. 2015 Jun;87(6):1013-20. doi: 10.1124/mol.114.097402. Epub 2015 Mar 30. PubMed PMID: 25824487. 10: Kanno Y, Tanuma N, Yatsu T, Li W, Koike K, Inouye Y. Nigramide J is a novel potent inverse agonist of the human constitutive androstane receptor. Pharmacol Res Perspect. 2014 Feb;2(1):2. doi: 10.1002/prp2.18. Epub 2014 Jan 26. PubMed PMID: 25505573; PubMed Central PMCID: PMC4186399. 11: Lim YP, Cheng CH, Chen WC, Chang SY, Hung DZ, Chen JJ, Wan L, Ma WC, Lin YH, Chen CY, Yokoi T, Nakajima M, Chen CJ. Allyl isothiocyanate (AITC) inhibits pregnane X receptor (PXR) and constitutive androstane receptor (CAR) activation and protects against acetaminophen- and amiodarone-induced cytotoxicity. Arch Toxicol. 2015 Jan;89(1):57-72. doi: 10.1007/s00204-014-1230-x. Epub 2014 Jul 29. PubMed PMID: 25069801. 12: Wang Y, Masuyama H, Nobumoto E, Zhang G, Hiramatsu Y. The inhibition of constitutive androstane receptor-mediated pathway enhances the effects of anticancer agents in ovarian cancer cells. Biochem Pharmacol. 2014 Aug 15;90(4):356-66. doi: 10.1016/j.bcp.2014.06.003. Epub 2014 Jun 10. PubMed PMID: 24928535. 13: Wahlang B, Falkner KC, Clair HB, Al-Eryani L, Prough RA, States JC, Coslo DM, Omiecinski CJ, Cave MC. Human receptor activation by aroclor 1260, a polychlorinated biphenyl mixture. Toxicol Sci. 2014 Aug 1;140(2):283-97. doi: 10.1093/toxsci/kfu083. Epub 2014 May 8. PubMed PMID: 24812009; PubMed Central PMCID: PMC4176050. 14: Wonganan P, Jonsson-Schmunk K, Callahan SM, Choi JH, Croyle MA. Evaluation of the HC-04 cell line as an in vitro model for mechanistic assessment of changes in hepatic cytochrome P450 3A during adenovirus infection. Drug Metab Dispos. 2014 Jul;42(7):1191-201. doi: 10.1124/dmd.113.056663. Epub 2014 Apr 24. PubMed PMID: 24764148; PubMed Central PMCID: PMC4053995. 15: Lau AJ, Chang TK. Fetal bovine serum and human constitutive androstane receptor: evidence for activation of the SV23 splice variant by artemisinin, artemether, and arteether in a serum-free cell culture system. Toxicol Appl Pharmacol. 2014 Jun 1;277(2):221-30. doi: 10.1016/j.taap.2014.03.023. Epub 2014 Apr 12. PubMed PMID: 24721719. 16: Yang H, Garzel B, Heyward S, Moeller T, Shapiro P, Wang H. Metformin represses drug-induced expression of CYP2B6 by modulating the constitutive androstane receptor signaling. Mol Pharmacol. 2014 Feb;85(2):249-60. doi: 10.1124/mol.113.089763. Epub 2013 Nov 19. PubMed PMID: 24252946; PubMed Central PMCID: PMC3913356. 17: Chen T, Laurenzana EM, Coslo DM, Chen F, Omiecinski CJ. Proteasomal interaction as a critical activity modulator of the human constitutive androstane receptor. Biochem J. 2014 Feb 15;458(1):95-107. doi: 10.1042/BJ20130685. PubMed PMID: 24224465; PubMed Central PMCID: PMC4019979. 18: Sueyoshi T, Li L, Wang H, Moore R, Kodavanti PR, Lehmler HJ, Negishi M, Birnbaum LS. Flame retardant BDE-47 effectively activates nuclear receptor CAR in human primary hepatocytes. Toxicol Sci. 2014 Feb;137(2):292-302. doi: 10.1093/toxsci/kft243. Epub 2013 Nov 11. PubMed PMID: 24218150; PubMed Central PMCID: PMC3908718. 19: Chen F, Zamule SM, Coslo DM, Chen T, Omiecinski CJ. The human constitutive androstane receptor promotes the differentiation and maturation of hepatic-like cells. Dev Biol. 2013 Dec 15;384(2):155-65. doi: 10.1016/j.ydbio.2013.10.012. Epub 2013 Oct 18. PubMed PMID: 24144921; PubMed Central PMCID: PMC3872969. 20: Paul KB, Thompson JT, Simmons SO, Vanden Heuvel JP, Crofton KM. Evidence for triclosan-induced activation of human and rodent xenobiotic nuclear receptors. Toxicol In Vitro. 2013 Oct;27(7):2049-60. doi: 10.1016/j.tiv.2013.07.008. Epub 2013 Jul 27. PubMed PMID: 23899473.