sp-i

PROTACKSP-IN-1 (Compound 21) is a spindle protein (KSP) degrader as a PROTAC, effectively degrading KSP in HCT-116 cells with a DC50 value of 114.8 nM. It inhibits the proliferation of HCT-116 with an IC50 of 10 nM, causes G2 M phase cell cycle arrest, and induces apoptosis in HCT-116. Additionally, PROTACKSP-IN-1 demonstrates antitumor activity in mouse models.

KSP-IA is a potent, specific, allosteric, and cell-active KSP inhibitor.

RASP-IN-1 (Compound A), a lipophilic compound, serves as an inhibitor for macular degeneration and exhibits biological activity within the rabbit retina. In a mouse model [1], the administration of 14 C-RASP-IN-1 (10 mg kg) intraperitoneally yielded a maximum concentration (C max) of 14.36 μg g in the posterior eye cup 30 minutes post-treatment.

Sp-cAMPS sodium salt is an analog of cAMP that serves as a potent activator of cAMP-dependent PKA I and PKA II, and as a competitive phosphodiesterase (PDE3A) inhibitor with a Ki of 47.6 μM. It also binds the PDE10 GAF domain with an EC50 of 40 μM [1] [2] [3].

Beauveriolide III, a cyclodepsipeptide found in Beauveria fungi, inhibits lipid droplet formation (at 3-10 μM) and cholesterol synthesis (IC50=0.41 μM). This compound also suppresses acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity (IC50=5.5 μM) and reduces atherosclerotic lesion size in Ldlr-/- and ApoE-/- mouse models (25-50 mg/kg).

I5B2 is a novel phosphorus-containing angiotensin I converting enzyme inhibitor. Angiotensin I converting enzyme is produced by Actinomadura sp.

Mitopodozide, as an ethylhydrazide derivative of podophyllic acid, acts as a mitotic poison in carcinomas of the ovary.

Benastatin A is a polyketide synthase-derived benastatin that has been found inStreptomycesand has diverse biological activities.1,2,3It inhibits glutathione S-transferase (GST; Ki= 5 μM for the rat liver enzyme).2Benastatin A is active against several bacteria, including methicillin-resistantS. aureus(MRSA; MIC = 3.12 μg ml). It induces apoptosis and cell cycle arrest at the G1 G0phase in Colon 26 mouse colon cancer cells when used at concentrations of 20 and 16 μM, respectively.3 1.Xu, Z., Schenk, A., and Hertweck, C.Molecular analysis of the benastatin biosynthetic pathway and genetic engineering of altered fatty acid-polyketide hybridsJ. Am. Chem. Soc.129(18)6022-6030(2007) 2.Aoyagi, T., Aoyama, T., Kojima, F., et al.Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. I. Taxonomy, production, isolation, physico-chemical properties and biological activitiesJ. Antibiot. (Tokyo)45(9)1385-1390(1992) 3.Kakizaki, I., Ookawa, K., Ishikawa, T., et al.Induction of apoptosis and cell cycle arrest in mouse colon 26 cells by benastatin AJpn. J. Cancer Res.91(11)1161-1168(2000)

Beauveriolide I is a cyclodepsipeptide that has been found inBeauveriaand an inhibitor of lipid droplet formation.1It inhibits lipid droplet formation when used at concentrations of 3 and 10 μM, as well as inhibits cholesterol synthesis (IC50= 0.78 μM), in primary mouse peritoneal macrophages.1,2Beauveriolide I also inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in mouse macrophage membranes (IC50= 6 μM).2 1.Namatame, I., Tomoda, H., Si, S., et al.Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979J. Antibiot. (Tokyo)52(1)1-6(1999) 2.Namatame, I., Tomoda, H., Ishibashi, S., et al.Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophagesProc. Nat. Acad. Sci. USA101(3)737-742(2004)

Terpendole I is a fungal metabolite that has been found in A. yamanashiensis.1 It is a weak inhibitor of acyl-coenzyme A:cholesterol acyltransferase (ACAT; IC50 = 145 μM) and is active against the bacteria B. cereus and B. subtilis (MICs = 100 μg/ml for both) but not S. aureus, P. aeruginosa, or K. pneumoniae (MICs = >200 μg/ml for all) or the fungus C. albicans (MIC = 200 μg/ml).1,2 It is cytotoxic to HeLa cells with an IC50 value of 52.6 μM.3 |1. Tomoda, H., Tabata, N., Yang, D.-J., et al. Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. III. Production, isolation and structure elucidation of new components. J. Antibiot. (Tokyo) 48(8), 793-804 (1995).|2. Zhao, J.-C., Wang, Y.-L., Zhang, T.-Y., et al. Indole diterpenoids from the endophytic fungus Drechmeria sp. as natural antimicrobial agents. Phytochemistry 148, 21-28 (2018).|3. Nagumo, Y., Motoyama, T., Hayashi, T., et al. Structure-activity relationships of terpendole E and its natural derivatives. ChemistrySelect 2(4), 1533-1536 (2017).

Heliquinomycin is a bacterial metabolite originally isolated fromStreptomycesthat has diverse biological activities.1It is active against a variety of Gram-positive bacteria, including strains ofB. anthracis, B. subtilis, and methicillin-sensitive or -resistantS. aureus(MICs = <0.05-0.39 μg/ml). Heliquinomycin inhibits the activity of DNA helicase with a Kivalue of 6.8 μM. It reduces the growth of L1210 leukemia, B16 melanoma, and FS-3 fibrosarcoma cells (IC50s = 0.97, 0.89, and 0.83 μg/ml, respectively). 1.Chino, M., Nishikawa, K., Umekita, M., et al.Heliquinomycin, a new inhibitor of DNA helicase, produced by Streptomyces sp. MJ929-SF2 I. Taxonomy, production, isolation, physico-chemical properties and biological activitiesJ. Antibiot. (Tokyo)49(8)752-757(1996)

Carbazomycin A is a bacterial metabolite that has been found in Streptomyces and has diverse biological activities.1,2It is active againstS. aureus,T. asteroides, andT. mentagrophytes(MIC = 12.5 μg ml for all), as well as the plant pathogenic fungusP. oryzae(MIC = 25 μg ml). Carbazomycin A is cytotoxic to MCF-7, KB, NCI H187, and Vero cells (IC50s = 26.2, 30.1, 18.4, and 32.6 μg ml, respectively).2 1.Sakano, K.-I., Ishimaru, K., and Nakamura, S.New antibiotics, carbazomycins A and B. I. Fermentation, extraction, purification and physico-chemical and biological propertiesJ Antibiot. (Tokyo)33(7)683-689(1980) 2.Intaraudom, C., Rachtawee, P., Suvannakad, R., et al.Antimalarial and antituberculosis substances from Streptomyces sp. BCC26924Tetrahedron67(39)7593-7597(2011)

Zelkovamycin is a cyclic peptide antibiotic isolated from Streptomyces, known to inhibit growth of X. oryzae, P. oryzae, S. aureus, and A. laidlawii in a concentration-dependent manner at concentrations ranging from 0.01 to 300 μg ml.

Sp-8-CPT-cAMPS is a powerful and specific cAMP analog that activates cAMP-dependent protein kinase A (PKA I and PKA II) selectively and effectively. It exhibits a 153-fold preference for site A of RI over site A of RII, and a 59-fold preference for site B of RII over site B of RI.

SN-28049 SN is a DNA intercalating drug that binds selectively to GC-rich DNA and shows curative activity against the Colon 38 adenocarcinoma in mice. SN 28049 has a complex action that may involve poisoning of topo IIalpha, suppression of topo I and inhibition of gene transcription from promoters with SP-1 sites. These actions may contribute to the promising experimental solid tumour anticancer activity of SN 28049.

Sp-cAMPS triethylamine, a cAMP analog, serves as a potent activator of cAMP-dependent PKA I and II, and acts as a competitive inhibitor of phosphodiesterase (PDE3A) with a K i of 47.6 µM. Additionally, it binds the PDE10 GAF domain with an EC 50 of 40 μM [1] [2] [3].

Sp-8-pCPT-PET-cGMPS acts as an activator of PKG-I. It is utilized in studying the role of the NO/NOS/sGC/PKG-I signaling pathway in cardiac differentiation.

Sp-8-Br-PET-cGMPS is a membrane-permeable PKG activator and an inhibitor of the membrane-permeable retinal cGMP-gated ion channels (cGMP-gated ion channel). It also serves as an activator for cGMP-dependent protein kinase I α and β. Resistant to mammalian cyclic nucleotide-dependent phosphodiesterases, Sp-8-Br-PET-cGMPS does not undergo metabolic side effects and exhibits stronger lipophilicity and permeability compared to Sp-8-pCPT-cGMPS. This compound is useful for investigating the role of the cGMP signaling pathway in the nervous system.

Sp-8-pCPT-cGMPS is a potent agonist for cyclic guanosine monophosphate-gated (CNG) channels and serves as a lipophilic activator for PKG (types I α, I β, and II) and PKA II. It exhibits excellent cell membrane permeability and stability against phosphodiesterases. This compound is utilized in studying the role of cGMP in synaptic transmission and neural plasticity.

Sp-8-PIP cAMP sodium, a non-corresponding isomer of 8-Piperidino-cAMP, demonstrates high-affinity binding at the regulatory subunit A site (AI) of cAMP-dependent protein kinase I. It acts as an antagonist for cAMP-induced activation.

F1839-I is a natural product from Stachybotrys sp.