Sangivamycin
(Synonyms: 桑霉素,NSC 65346; BA-90912) 目录号 : GC63439
Sangivamycin (NSC 65346) 是一种核苷类似物，是蛋白激酶C (PKC) 的有效抑制剂，Ki 为 10 μM。Sangivamycin 对多种人类癌症具有有效的抗增殖活性。
Cas No.:18417-89-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Sangivamycin (NSC 65346), a nucleoside analog, is a potent inhibitor of protein kinase C (PKC) with an Ki of 10 μM. Sangivamycin has potent antiproliferative activity against a variety of human cancers[1][2].
Sangivamycin has differential antitumor effects in drug-sensitive MCF7/wild type (WT) cells, causing growth arrest, and in multidrug-resistant MCF7/adriamycin-resistant (ADR) human breast carcinoma cells, causing massive apoptotic cell death[2].Sangivamycin (0.3 μM; 0-72 hours), shows almost maximal cytocidal (for MCF7/ADR) or cytostatic (for MCF7/WT) effects[2].Sangivamycin activates caspases in MCF7/ADR cells. Upon exposure of MCF7/ADR cells to Sangivamycin (0.3 μM;), a vast amount of cleavage of lamin A to a 28-kDa fragment is detected within 48 hours[2].
[1]. Loomis CR, Bell RM. Sangivamycin, a nucleoside analogue, is a potent inhibitor of protein kinase C. J Biol Chem. 1988;263(4):1682-1692.
[2]. Lee SA, et al. The nucleoside analog sangivamycin induces apoptotic cell death in breast carcinoma MCF7/adriamycin-resistant cells via protein kinase Cdelta and JNK activation. J Biol Chem. 2007;282(20):15271-15283.
| Cas No. | 18417-89-5 | SDF | |
| 别名 | 桑霉素,NSC 65346; BA-90912 | ||
| 分子式 | C12H15N5O5 | 分子量 | 309.28 |
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.2333 mL | 16.1666 mL | 32.3332 mL |
| 5 mM | 0.6467 mL | 3.2333 mL | 6.4666 mL |
| 10 mM | 0.3233 mL | 1.6167 mL | 3.2333 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Sangivamycin is highly effective against SARS-CoV-2 in vitro and has favorable drug properties
JCI Insight 2022 Jan 11;7(1):e153165.PMID:34807849DOI:10.1172/jci.insight.153165.
Sangivamycin is a nucleoside analog that is well tolerated by humans and broadly active against phylogenetically distinct viruses, including arenaviruses, filoviruses, and orthopoxviruses. Here, we show that Sangivamycin is a potent antiviral against multiple variants of replicative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with half-maximal inhibitory concentration in the nanomolar range in several cell types. Sangivamycin suppressed SARS-CoV-2 replication with greater efficacy than remdesivir (another broad-spectrum nucleoside analog). When we investigated Sangivamycin's potential for clinical administration, pharmacokinetic; absorption, distribution, metabolism, and excretion (ADME); and toxicity properties were found to be favorable. When tested in combination with remdesivir, efficacy was additive rather than competitive against SARS-CoV-2. The proven safety in humans, long half-life, potent antiviral activity (compared to remdesivir), and combinatorial potential suggest that Sangivamycin is likely to be efficacious alone or in combination therapy to suppress viremia in patients. Sangivamycin may also have the ability to help combat drug-resistant or vaccine-escaping SARS-CoV-2 variants since it is antivirally active against several tested variants. Our results support the pursuit of Sangivamycin for further preclinical and clinical development as a potential coronavirus disease 2019 therapeutic.
Sangivamycin induces apoptosis by suppressing Erk signaling in primary effusion lymphoma cells
Biochem Biophys Res Commun 2014 Feb 7;444(2):135-40.PMID:24434142DOI:10.1016/j.bbrc.2014.01.017.
Sangivamycin, a structural analog of adenosine and antibiotic exhibiting antitumor and antivirus activities, inhibits protein kinase C and the synthesis of both DNA and RNA. Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by Kaposi's sarcoma-associated herpesvirus (KSHV) in immunosuppressed patients and HIV-infected homosexual males. PEL cells are derived from post-germinal center B cells, and are infected with KSHV. Herein, we asked if Sangivamycin might be useful to treat PEL. We found that Sangivamycin killed PEL cells, and we explored the underlying mechanism. Sangivamycin treatment drastically decreased the viability of PEL cell lines compared to KSHV-uninfected B lymphoma cell lines. Sangivamycin induced the apoptosis of PEL cells by activating caspase-7 and -9. Further, Sangivamycin suppressed the phosphorylation of Erk1/2 and Akt, thus inhibiting activation of the proteins. Inhibitors of Akt and MEK suppressed the proliferation of PEL cells compared to KSHV-uninfected cells. It is known that activation of Erk and Akt signaling inhibits apoptosis and promotes proliferation in PEL cells. Our data therefore suggest that Sangivamycin induces apoptosis by inhibiting Erk and Akt signaling in such cells. We next investigated whether Sangivamycin, in combination with an HSP90 inhibitor geldanamycin (GA) or valproate (valproic acid), potentiated the cytotoxic effects of the latter drugs on PEL cells. Compared to treatment with GA or valproate alone, the addition of Sangivamycin enhanced cytotoxic activity. Our data thus indicate that Sangivamycin may find clinical utility as a novel anti-cancer agent targeting PEL.
Sangivamycin and its derivatives inhibit Haspin-Histone H3-survivin signaling and induce pancreatic cancer cell death
Sci Rep 2019 Nov 12;9(1):16588.PMID:31719634DOI:10.1038/s41598-019-53223-0.
Current treatment options for patients with pancreatic cancer are suboptimal, resulting in a five year survival rate of about 9%. Difficulties with treatment are due to an immunosuppressive, fibrotic tumor microenvironment that prevents drugs from reaching tumor cells, but also to the limited efficacy of existing FDA-approved chemotherapeutic compounds. We here show that the nucleoside analog Sangivamycin and its closely-related compound Toyocamycin target PDA cell lines, and are significantly more efficient than Gemcitabine. Using KINOMEscan screening, we identified the kinase Haspin, which is overexpressed in PDA cell lines and human PDA samples, as a main target for both compounds. Inhibition of Haspin leads to a decrease in Histone H3 phosphorylation and prevents Histone H3 binding to survivin, thus providing mechanistic insight of how Sangivamycin targets cell proliferation, mitosis and induces apoptotic cell death. In orthotopically implanted tumors in mice, Sangivamycin was efficient in decreasing the growth of established tumors. In summary, we show that Sangivamycin and derivatives can be an efficient new option for treatment of PDA.
Sangivamycin, a nucleoside analogue, is a potent inhibitor of protein kinase C
J Biol Chem 1988 Feb 5;263(4):1682-92.PMID:3338987doi
Protein kinase C functions prominently in cell regulation via its pleiotropic role in signal transduction processes. Certain oncogene products resemble elements involved in transmembrane signaling, elevate cellular sn-1,2-diacylglycerol second messenger levels, and activate protein kinase C. Sangivamycin was unique among the nucleoside compounds tested in its ability to potently inhibit protein kinase C activity. Inhibition was competitive with respect to ATP for both protein kinase C and the catalytic fragment of protein kinase C prepared by trypsin digestion. Sangivamycin was a noncompetitive inhibitor with respect to histone and lipid cofactors (phosphatidylserine and diacylglycerol). Sangivamycin inhibited native protein kinase C and the catalytic fragment identically, with apparent Ki values of 11 and 15 microM, respectively. Sangivamycin was an effective an inhibitor of protein kinase C as H-7, an isoquinolinsulfonamide. Sangivamycin did not inhibit [3H]phorbol-12,13-dibutyrate binding to protein kinase C. Sangivamycin did not exert its action through the lipid binding/regulatory domain; inhibition was not affected by the presence of lipid or detergent. Unlike H-7, Sangivamycin selectively inhibited protein kinase C compared to cAMP-dependent protein kinase. The discovery that protein kinase C is inhibited by Sangivamycin and other antitumor agents suggests that protein kinase C may be a target for rational design of antitumor compounds.
The nucleoside analog Sangivamycin induces apoptotic cell death in breast carcinoma MCF7/adriamycin-resistant cells via protein kinase Cdelta and JNK activation
J Biol Chem 2007 May 18;282(20):15271-83.PMID:17371872DOI:10.1074/jbc.M701362200.
Sangivamycin has shown a potent antiproliferative activity against a variety of human cancers. However, little is known about the mechanism of action underlying its antitumor activity. Here we demonstrate that Sangivamycin has differential antitumor effects in drug-sensitive MCF7/wild type (WT) cells, causing growth arrest, and in multidrug-resistant MCF7/adriamycin-resistant (ADR) human breast carcinoma cells, causing massive apoptotic cell death. Comparisons between the effects of Sangivamycin on these two cell lines allowed us to identify the mechanism underlying the apoptotic antitumor effect. Fluorescence-activated cell sorter analysis indicated that Sangivamycin induced cell cycle arrest in the G(2)/M phase in MCF7/ADR cells. A marked induction of c-Jun expression as well as phosphorylation of c-Jun and JNK was observed after Sangivamycin treatment of MCF7/ADR cells but not MCF7/WT cells. Sangivamycin also induced cleavage of lamin A and poly(ADP-ribose) polymerase (PARP) in MCF7/ADR cells, probably via activation of caspase-6, -7, and -9. Pretreatment with a caspase-9-specific inhibitor or pan-caspase inhibitor abolished sangivamycin-induced cleavage of lamin A and PARP but not Sangivamycin induction of c-Jun expression and phosphorylation. Pretreatment of MCF7/ADR cells with SP600125, a specific inhibitor of JNK, or with rottlerin, a specific inhibitor of protein kinase Cdelta (PKCdelta), significantly reduced the sangivamycin-induced apoptosis and almost completely abolished sangivamycin-induced phosphorylation of c-Jun and cleavage of lamin A and PARP. Transfection of MCF7/ADR cells with PKCdelta small interfering RNAs or PKCdelta antibody or rottlerin pretreatment significantly suppressed the phosphorylation of JNK. Taken together, our data suggest that Sangivamycin induces mitochondria-mediated apoptotic cell death of MCF7/ADR cells via activation of JNK in a protein kinase Cdelta-dependent manner.