Sapacitabine | CYC-682 | CAS#151823-14-2 | nucleoside analogue

MedKoo Cat#: 202560 | Name: Sapacitabine

Description:

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

Sapacitabine is an orally bioavailable pyrimidine analogue prodrug with potential antineoplastic activity. Sapacitabine is hydrolyzed by amidases to the deoxycytosine analogue CNDAC (2'-Cyano-2'-deoxyarabinofuranosylcytosine), which is then phosphorylated into the active triphosphate form.

Chemical Structure

Sapacitabine

CAS#151823-14-2

Theoretical Analysis

MedKoo Cat#: 202560

Name: Sapacitabine

CAS#: 151823-14-2

Chemical Formula: C26H42N4O5

Exact Mass: 490.3155

Molecular Weight: 490.64

Elemental Analysis: C, 63.65; H, 8.63; N, 11.42; O, 16.30

Price and Availability

Size	Price	Availability
5mg	USD 375.00	2 Weeks
10mg	USD 600.00	2 Weeks
25mg	USD 850.00	2 Weeks
50mg	USD 1,250.00	2 Weeks

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Related CAS #

No Data

Synonym

CS682; CYC682; CYC-682; Sapacitabine

IUPAC/Chemical Name

N-(1-((2R,3S,4S,5R)-3-cyano-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)palmitamide

InChi Key

LBGFKUUHOPIEMA-PEARBKPGSA-N

InChi Code

InChI=1S/C26H42N4O5/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-23(32)28-22-16-17-30(26(34)29-22)25-20(18-27)24(33)21(19-31)35-25/h16-17,20-21,24-25,31,33H,2-15,19H2,1H3,(H,28,29,32,34)/t20-,21+,24-,25+/m0/s1

SMILES Code

CCCCCCCCCCCCCCCC(NC(C=CN1[C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2C#N)=NC1=O)=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, not soluble in water.

Shelf Life

>5 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

Both sapacitabine and its major metabolite, CNDAC, have demonstrated potent anti-tumor activity in both blood and solid tumors in preclinical studies. In a liver metastatic mouse model, sapacitabine was shown to be superior to gemcitabine (GemzarÂ®; Lilly) or 5-FU, two widely used nucleoside analogs, in delaying the onset and growth of liver metastasis. Cyclacel has initiated a number of clinical trials to evaluate sapacitabine in both solid and hematological tumors laying the foundation for future Phase 2 studies and combination studies with other anti-cancer agents. Three Phase 1 studies have been completed, which evaluated safety and pharmacokinetics of a variety of dosing schedules in approximately 120 patients with solid tumors. Sapacitabine is currently being evaluated in two Phase 2 trials in patients with advanced cutaneous T-cell lymphoma (CTCL) and in elderly patients with acute myeloid leukemias (AML). See http://www.cyclacel.com/cyc/rd/programs/oncology/sapacitabine/ .

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Sapacitabine is a nucleoside analog prodrug of CNDAC, causing single-strand DNA breaks and inducing arrest of the cell division cycle at the G2 phase.

In vitro activity:

Sapacitabine exhibits promising antiproliferative activity across various cell lines, including ones resistant to other anticancer drugs. Sapacitabine is cytotoxic to dCK-deficient L1210 cells, suggesting potential alternative mechanisms of action in certain cases. This makes sapacitabine a strong candidate for further evaluation in combination treatments with existing anticancer agents. Reference: Br J Cancer. 2007 Sep 3;97(5):628-36. https://pubmed.ncbi.nlm.nih.gov/17637678/

In vivo activity:

Orally administered Sapacitabine showed a more potent activity against human tumor xenografts than CNDAC. Moreover, Sapacitabine was effective against various human organ tumor xenografts at a wide dose range and with low toxicity, and was effective against P388 leukemic cells resistant to mitomycin-C, vincristine, 5-fluorouracil or cisplatin in syngeneic mice. Reference: Int J Cancer. 1999 Jul 19;82(2):226-36. https://pubmed.ncbi.nlm.nih.gov/10389757/

	Solvent	mg/mL	mM
Solubility
	DMSO	33.3	67.93

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 490.64 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. Green SR, Choudhary AK, Fleming IN. Combination of sapacitabine and HDAC inhibitors stimulates cell death in AML and other tumour types. Br J Cancer. 2010 Oct 26;103(9):1391-9. doi: 10.1038/sj.bjc.6605922. Epub 2010 Oct 5. PMID: 20924380; PMCID: PMC2990608. 2. Serova M, Galmarini CM, Ghoul A, Benhadji K, Green SR, Chiao J, Faivre S, Cvitkovic E, Le Tourneau C, Calvo F, Raymond E. Antiproliferative effects of sapacitabine (CYC682), a novel 2'-deoxycytidine-derivative, in human cancer cells. Br J Cancer. 2007 Sep 3;97(5):628-36. doi: 10.1038/sj.bjc.6603896. Epub 2007 Jul 17. PMID: 17637678; PMCID: PMC2360357. 3. Kantarjian HM, Begna KH, Altman JK, Goldberg SL, Sekeres MA, Strickland SA, Arellano ML, Claxton DF, Baer MR, Gautier M, Berman E, Seiter K, Solomon SR, Schiller GJ, Luger SM, Butrym A, Gaidano G, Thomas XG, Montesinos P, Rizzieri DA, Quick DP, Venugopal P, Gaur R, Maness LJ, Kadia TM, Ravandi F, Buyse ME, Chiao JH. Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS). Cancer. 2021 Dec 1;127(23):4421-4431. doi: 10.1002/cncr.33828. Epub 2021 Aug 23. PMID: 34424530; PMCID: PMC9523989. 4. Hanaoka K, Suzuki M, Kobayashi T, Tanzawa F, Tanaka K, Shibayama T, Miura S, Ikeda T, Iwabuchi H, Nakagawa A, Mitsuhashi Y, Hisaoka M, Kaneko M, Tomida A, Wataya Y, Nomura T, Sasaki T, Matsuda A, Tsuruo T, Kurakata S. Antitumor activity and novel DNA-self-strand-breaking mechanism of CNDAC (1-(2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl) cytosine) and its N4-palmitoyl derivative (CS-682). Int J Cancer. 1999 Jul 19;82(2):226-36. doi: 10.1002/(sici)1097-0215(19990719)82:2<226::aid-ijc13>3.0.co;2-x. PMID: 10389757.

In vitro protocol:

In vivo protocol:

1. Kantarjian HM, Begna KH, Altman JK, Goldberg SL, Sekeres MA, Strickland SA, Arellano ML, Claxton DF, Baer MR, Gautier M, Berman E, Seiter K, Solomon SR, Schiller GJ, Luger SM, Butrym A, Gaidano G, Thomas XG, Montesinos P, Rizzieri DA, Quick DP, Venugopal P, Gaur R, Maness LJ, Kadia TM, Ravandi F, Buyse ME, Chiao JH. Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS). Cancer. 2021 Dec 1;127(23):4421-4431. doi: 10.1002/cncr.33828. Epub 2021 Aug 23. PMID: 34424530; PMCID: PMC9523989. 2. Hanaoka K, Suzuki M, Kobayashi T, Tanzawa F, Tanaka K, Shibayama T, Miura S, Ikeda T, Iwabuchi H, Nakagawa A, Mitsuhashi Y, Hisaoka M, Kaneko M, Tomida A, Wataya Y, Nomura T, Sasaki T, Matsuda A, Tsuruo T, Kurakata S. Antitumor activity and novel DNA-self-strand-breaking mechanism of CNDAC (1-(2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl) cytosine) and its N4-palmitoyl derivative (CS-682). Int J Cancer. 1999 Jul 19;82(2):226-36. doi: 10.1002/(sici)1097-0215(19990719)82:2<226::aid-ijc13>3.0.co;2-x. PMID: 10389757.

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PMID: 38920407; PMCID: PMC11264598. 3: Meric-Bernstam F, Lloyd MW, Koc S, Evrard YA, McShane LM, Lewis MT, Evans KW, Li D, Rubinstein L, Welm A, Dean DA 2nd, Srivastava A, Grover JW, Ha MJ, Chen H, Huang X, Varadarajan K, Wang J, Roth JA, Welm B, Govinden R, Ding L, Kaochar S, Mitsiades N, Carvajal-Carmona L, Herylyn M, Davies MA, Shapiro GI, Fields R, Trevino JG, Harrell JC; NCI PDXNet Consortium; Doroshow JH, Chuang JH, Moscow JA. Assessment of Patient-Derived Xenograft Growth and Antitumor Activity: The NCI PDXNet Consensus Recommendations. Mol Cancer Ther. 2024 Jul 2;23(7):924-938. doi: 10.1158/1535-7163.MCT-23-0471. PMID: 38641411; PMCID: PMC11217730. 4: Konstantinopoulos PA, Cheng SC, Lee EK, da Costa AABA, Gulhan D, Wahner Hendrickson AE, Kochupurakkal B, Kolin DL, Kohn EC, Liu JF, Penson RT, Stover EH, Curtis J, Sawyer H, Polak M, Chowdhury D, D'Andrea AD, Färkkilä A, Shapiro GI, Matulonis UA. 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