CD437 | CAS# 125316-60-1 | RARγ Agonist

MedKoo Cat#: 532771 | Name: CD437

Description:

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

CD437 is a synthetic retinoid that is an RARγ-selective agonist. It displays RARγ-dependent and -independent effects on differentiation and apoptosis. CD437 induces apoptosis and acts synergistically with TRAIL receptor-2 agonist in malignant melanoma. CD437 inhibits DNA replication in cells and recombinant POLA1 activity in vitro.

Chemical Structure

CD437

CAS# 125316-60-1

Theoretical Analysis

MedKoo Cat#: 532771

Name: CD437

CAS#: 125316-60-1

Chemical Formula: C27H26O3

Exact Mass: 398.1882

Molecular Weight: 398.50

Elemental Analysis: C, 81.38; H, 6.58; O, 12.04

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,850.00	2 Weeks
2g	USD 6,350.00	2 Weeks

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Synonym

CD437; CD 437; CD-437; Ro-472077; Ro 472077; Ro472077; AHPN

IUPAC/Chemical Name

6-[3-(1-adamantyl)-4-hydroxyphenyl]naphthalene-2-carboxylic acid

InChi Key

LDGIHZJOIQSHPB-UHFFFAOYSA-N

InChi Code

InChI=1S/C27H26O3/c28-25-6-5-22(20-1-2-21-11-23(26(29)30)4-3-19(21)10-20)12-24(25)27-13-16-7-17(14-27)9-18(8-16)15-27/h1-6,10-12,16-18,28H,7-9,13-15H2,(H,29,30)

SMILES Code

O=C(C1=CC=C2C=C(C3=CC=C(O)C(C45CC6CC(C5)CC(C6)C4)=C3)C=CC2=C1)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:

CD437 is a selective Retinoic Acid Receptor γ (RARγ) agonist.

In vitro activity:

A synthetic retinoid, CD437, has been shown to exert potent anti-tumor activity against various types of cancer cell lines, regardless of their sensitivities to natural retinoids. It was herein demonstrated that CD437 induces endoplasmic reticulum (ER) stress, including the up-regulation of CHOP, BIP and GADD34 mRNA through ER stress transducer (PERK and IRE1alpha) activation in an ovarian adenocarcinoma cell line, SKOV3. It was also shown that CD437 induced the CHOP and GADD34 expressions in another four ovarian adenocarcinoma cell lines, indicating that CD437 functions as an ER stress inducer in these cell lines. Moreover, the siRNA-mediated knockdown of inducible CHOP expression prevented the cytotoxic effect of CD437. These results suggest that ER stress plays an important role in the mechanism by which CD437 induces apoptosis in ovarian adenocarcinoma cells. Reference: Biochem Biophys Res Commun. 2008 Feb 15;366(3):840-7. https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(07)02657-5

In vivo activity:

CD437 also exhibited a strong growth inhibitory effect on MeWo melanoma cells in a xenograft model. In tissue sections of CD437-treated MeWo tumors from these animals, apoptotic melanoma cells and c-fos overexpressing cells were colocalized by TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) staining and in situ hybridization. Taken together, this report identifies CD437 as a retinoid that activates and upregulates the transcription factor AP-1, leading eventually to programmed cell death of exposed human melanoma cells in vitro and in vivo. Reference: J Cell Biol. 1996 Dec;135(6 Pt 2):1889-98. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/8991099/

	Solvent	mg/mL	mM
Solubility
	DMSO	150.0	376.42

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 398.50 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:

In vitro protocol:

1. Watanabe Y, Tsuchiya H, Sakabe T, Matsuoka S, Akechi Y, Fujimoto Y, Yamane K, Ikeda R, Nishio R, Terabayashi K, Ishii K, Gonda K, Matsumi Y, Ashla AA, Okamoto H, Takubo K, Tomita A, Hoshikawa Y, Kurimasa A, Itamochi H, Harada T, Terakawa N, Shiota G. CD437 induces apoptosis in ovarian adenocarcinoma cells via ER stress signaling. Biochem Biophys Res Commun. 2008 Feb 15;366(3):840-7. doi: 10.1016/j.bbrc.2007.12.028. Epub 2007 Dec 17. PMID: 18082618. 2. Han T, Goralski M, Capota E, Padrick SB, Kim J, Xie Y, Nijhawan D. The antitumor toxin CD437 is a direct inhibitor of DNA polymerase α. Nat Chem Biol. 2016 Jul;12(7):511-5. doi: 10.1038/nchembio.2082. Epub 2016 May 16. PMID: 27182663; PMCID: PMC4912453.

In vivo protocol:

1. Schadendorf D, Kern MA, Artuc M, Pahl HL, Rosenbach T, Fichtner I, Nürnberg W, Stüting S, von Stebut E, Worm M, Makki A, Jurgovsky K, Kolde G, Henz BM. Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo. J Cell Biol. 1996 Dec;135(6 Pt 2):1889-98. doi: 10.1083/jcb.135.6.1889. PMID: 8991099; PMCID: PMC2133968. 2. Parrella E, Giannì M, Fratelli M, Barzago MM, Raska I Jr, Diomede L, Kurosaki M, Pisano C, Carminati P, Merlini L, Dallavalle S, Tavecchio M, Rochette-Egly C, Terao M, Garattini E. Antitumor activity of the retinoid-related molecules (E)-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) in F9 teratocarcinoma: Role of retinoic acid receptor gamma and retinoid-independent pathways. Mol Pharmacol. 2006 Sep;70(3):909-24. doi: 10.1124/mol.106.023614. Epub 2006 Jun 20. PMID: 16788091.

1: Han T, Goralski M, Capota E, Padrick SB, Kim J, Xie Y, Nijhawan D. The antitumor toxin CD437 is a direct inhibitor of DNA polymerase α. Nat Chem Biol. 2016 Jul;12(7):511-5. doi: 10.1038/nchembio.2082. Epub 2016 May 16. PubMed PMID: 27182663; PubMed Central PMCID: PMC4912453. 2: Magnussen GI, Ree Rosnes AK, Shahzidi S, Dong HP, Emilsen E, Engesæter B, Flørenes VA. Synthetic retinoid CD437 induces apoptosis and acts synergistically with TRAIL receptor-2 agonist in malignant melanoma. Biochem Biophys Res Commun. 2012 Apr 13;420(3):516-22. doi: 10.1016/j.bbrc.2012.03.023. Epub 2012 Mar 13. PubMed PMID: 22446330. 3: Mishur RJ, Griffin ME, Battle CH, Shan B, Jayawickramarajah J. Molecular recognition and enhancement of aqueous solubility and bioactivity of CD437 by β-cyclodextrin. Bioorg Med Chem Lett. 2011 Jan 15;21(2):857-60. doi: 10.1016/j.bmcl.2010.11.073. Epub 2010 Nov 21. PubMed PMID: 21185186; PubMed Central PMCID: PMC3057113. 4: Hashiguchi K, Tsuchiya H, Tomita A, Ueda C, Akechi Y, Sakabe T, Kurimasa A, Nozaki M, Yamada T, Tsuchida S, Shiota G. Involvement of ETS1 in thioredoxin-binding protein 2 transcription induced by a synthetic retinoid CD437 in human osteosarcoma cells. Biochem Biophys Res Commun. 2010 Jan 1;391(1):621-6. doi: 10.1016/j.bbrc.2009.11.109. Epub 2009 Nov 20. PubMed PMID: 19932085. 5: Matsuoka S, Tsuchiya H, Sakabe T, Watanabe Y, Hoshikawa Y, Kurimasa A, Itamochi H, Harada T, Terakawa N, Masutani H, Yodoi J, Shiota G. Involvement of thioredoxin-binding protein 2 in the antitumor activity of CD437. Cancer Sci. 2008 Dec;99(12):2485-90. doi: 10.1111/j.1349-7006.2008.00979.x. Epub 2008 Nov 17. PubMed PMID: 19018770. 6: Pan M, Geng S, Xiao S, Ren J, Liu Y, Li X, Li Z, Peng Z. Apoptosis induced by synthetic retinoic acid CD437 on human melanoma A375 cells involves RIG-I pathway. Arch Dermatol Res. 2009 Jan;301(1):15-20. doi: 10.1007/s00403-008-0902-x. Epub 2008 Oct 21. PubMed PMID: 18936944. 7: Valli C, Paroni G, Di Francesco AM, Riccardi R, Tavecchio M, Erba E, Boldetti A, Gianni' M, Fratelli M, Pisano C, Merlini L, Antoccia A, Cenciarelli C, Terao M, Garattini E. Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity. Mol Cancer Ther. 2008 Sep;7(9):2941-54. doi: 10.1158/1535-7163.MCT-08-0419. PubMed PMID: 18790775. 8: Gonda K, Tsuchiya H, Sakabe T, Akechi Y, Ikeda R, Nishio R, Terabayashi K, Ishii K, Matsumi Y, Ashla AA, Okamoto H, Takubo K, Matsuoka S, Watanabe Y, Hoshikawa Y, Kurimasa A, Shiota G. Synthetic retinoid CD437 induces mitochondria-mediated apoptosis in hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2008 Jun 13;370(4):629-33. doi: 10.1016/j.bbrc.2008.04.008. Epub 2008 Apr 10. PubMed PMID: 18406343. 9: Pan M, Peng ZH, Xiao SX, Li XL, Liu Y, Li ZX, Ren JW. [A novel retinoid CD437 induces apoptosis of human epidermoid carcinoma A431 cells]. Nan Fang Yi Ke Da Xue Xue Bao. 2008 Mar;28(3):305-8. Chinese. PubMed PMID: 18359678. 10: Watanabe Y, Tsuchiya H, Sakabe T, Matsuoka S, Akechi Y, Fujimoto Y, Yamane K, Ikeda R, Nishio R, Terabayashi K, Ishii K, Gonda K, Matsumi Y, Ashla AA, Okamoto H, Takubo K, Tomita A, Hoshikawa Y, Kurimasa A, Itamochi H, Harada T, Terakawa N, Shiota G. CD437 induces apoptosis in ovarian adenocarcinoma cells via ER stress signaling. Biochem Biophys Res Commun. 2008 Feb 15;366(3):840-7. Epub 2007 Dec 17. PubMed PMID: 18082618. 11: Jiang T, Soprano DR, Soprano KJ. GADD45A is a mediator of CD437 induced apoptosis in ovarian carcinoma cells. J Cell Physiol. 2007 Sep;212(3):771-9. PubMed PMID: 17474084. 12: Parrella E, Giannì M, Fratelli M, Barzago MM, Raska I Jr, Diomede L, Kurosaki M, Pisano C, Carminati P, Merlini L, Dallavalle S, Tavecchio M, Rochette-Egly C, Terao M, Garattini E. Antitumor activity of the retinoid-related molecules (E)-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) in F9 teratocarcinoma: Role of retinoic acid receptor gamma and retinoid-independent pathways. Mol Pharmacol. 2006 Sep;70(3):909-24. Epub 2006 Jun 20. PubMed PMID: 16788091. 13: Zou C, Zhou J, Qian L, Feugang JM, Liu J, Wang X, Wu S, Ding H, Zou C, Liebert M, Grossman HB. Comparing the effect of ATRA, 4-HPR, and CD437 in bladder cancer cells. Front Biosci. 2006 Sep 1;11:2007-16. PubMed PMID: 16720286. 14: Jin F, Liu X, Zhou Z, Yue P, Lotan R, Khuri FR, Chung LW, Sun SY. Activation of nuclear factor-kappaB contributes to induction of death receptors and apoptosis by the synthetic retinoid CD437 in DU145 human prostate cancer cells. Cancer Res. 2005 Jul 15;65(14):6354-63. PubMed PMID: 16024638. 15: Boisvieux-Ulrich E, Sourdeval M, Marano F. CD437, a synthetic retinoid, induces apoptosis in human respiratory epithelial cells via caspase-independent mitochondrial and caspase-8-dependent pathways both up-regulated by JNK signaling pathway. Exp Cell Res. 2005 Jul 1;307(1):76-90. Epub 2005 Apr 18. PubMed PMID: 15922728. 16: Kim HJ, Lotan R. Identification of protein modulation by the synthetic retinoid CD437 in lung carcinoma cells using high throughput immunoblotting. Int J Oncol. 2005 Feb;26(2):483-91. PubMed PMID: 15645134. 17: Holmes WF, Soprano DR, Soprano KJ. Early events in the induction of apoptosis in ovarian carcinoma cells by CD437: activation of the p38 MAP kinase signal pathway. Oncogene. 2003 Sep 25;22(41):6377-86. PubMed PMID: 14508518. 18: Rishi AK, Zhang L, Boyanapalli M, Wali A, Mohammad RM, Yu Y, Fontana JA, Hatfield JS, Dawson MI, Majumdar AP, Reichert U. Identification and characterization of a cell cycle and apoptosis regulatory protein-1 as a novel mediator of apoptosis signaling by retinoid CD437. J Biol Chem. 2003 Aug 29;278(35):33422-35. Epub 2003 Jun 18. PubMed PMID: 12816952. 19: Holmes WF, Soprano DR, Soprano KJ. Comparison of the mechanism of induction of apoptosis in ovarian carcinoma cells by the conformationally restricted synthetic retinoids CD437 and 4-HPR. J Cell Biochem. 2003 May 15;89(2):262-78. PubMed PMID: 12704790. 20: Joseph B, Marchetti P, Lefebvre O, Schraen-Maschke S, Méreau-Richard C, Formstecher P. The novel retinoid AHPN/CD437 induces a rapid but incomplete apoptotic response in human myeloma cells. Biochim Biophys Acta. 2003 Feb 17;1593(2-3):277-82. PubMed PMID: 12581872.