Sangivamycin
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| Category | Antibiotics |
| Catalog number | BBF-03450 |
| CAS | 18417-89-5 |
| Molecular Weight | 309.28 |
| Molecular Formula | C12H15N5O5 |
| Purity | 95% |
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Description
Sangivamycin is a nucleoside (purine) antibiotic produced by the strain of Str. rimosus BA-90912. 0.02-0.05 μg/mL of Sangivamycin inhibits HeLa cells. It has weak inhibitory effect on sarcoma-180 and adenocarcinoma 755 in mice. It has obvious inhibitory effect on leukemia L-1210. When intraperitoneally administered, the drug binds to nucleic acids in tissues in mice through phosphorylation.
Specification
| Related CAS | 21090-35-7 (hydrochloride) |
| Synonyms | 4-Amino-7-β-D-ribofuranosyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide; 7-Deazaadenosine-7-carboxamide; NSC 65346; Antibiotic B-14437; Ara-sangivamycin |
| Storage | Store at 2-8°C under inert atmosphere |
| IUPAC Name | 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrrolo[2,3-d]pyrimidine-5-carboxamide |
| Canonical SMILES | C1=C(C2=C(N=CN=C2N1C3C(C(C(O3)CO)O)O)N)C(=O)N |
| InChI | InChI=1S/C12H15N5O5/c13-9-6-4(10(14)21)1-17(11(6)16-3-15-9)12-8(20)7(19)5(2-18)22-12/h1,3,5,7-8,12,18-20H,2H2,(H2,14,21)(H2,13,15,16)/t5-,7-,8-,12-/m1/s1 |
| InChI Key | OBZJZDHRXBKKTJ-JTFADIMSSA-N |
Properties
| Appearance | White to Off-white Solid |
| Application | Antibiotics, Antineoplastic |
| Antibiotic Activity Spectrum | Neoplastics (Tumor) |
| Boiling Point | 880.6°C at 760 mmHg |
| Melting Point | 258-260°C |
| Density | 1.3120 g/cm3 (Predicted) |
| Solubility | Soluble in Methanol |
Reference Reading
1. Sangivamycin and its derivatives inhibit Haspin-Histone H3-survivin signaling and induce pancreatic cancer cell death
Ligia I Bastea, Laeticia M A Hollant, Heike R Döppler, Elizabeth M Reid, Peter Storz Sci Rep. 2019 Nov 12;9(1):16588. doi: 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.
2. Sangivamycin induces apoptosis by suppressing Erk signaling in primary effusion lymphoma cells
Kazufumi Wakao, Tadashi Watanabe, Tadatoshi Takadama, Sadaharu Ui, Zenpei Shigemi, Hiroki Kagawa, Chizuka Higashi, Rie Ohga, Takahiro Taira, Masahiro Fujimuro Biochem Biophys Res Commun. 2014 Feb 7;444(2):135-40. doi: 10.1016/j.bbrc.2014.01.017. Epub 2014 Jan 14.
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.
3. Sangivamycin is highly effective against SARS-CoV-2 in vitro and has favorable drug properties
Ryan P Bennett, Elena N Postnikova, Brett P Eaton, Yingyun Cai, Shuiqing Yu, Charles O Smith, Janie Liang, Huanying Zhou, Gregory A Kocher, Michael J Murphy, Harold C Smith, Jens H Kuhn JCI Insight. 2022 Jan 11;7(1):e153165. doi: 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.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
