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| Product | Description | |
|---|---|---|
| 2-Chlorohexadecanoic acid | 2-Chlorohexadecanoic acid, an inflammatory lipid mediator, interferes with protein palmitoylation,induces ER-stress markers, reduced the ER ATP content, and activates transcription and secretion of IL-6 as well as IL-8.2-Chlorohexadecanoic acid disrupts the mitochondrial membrane potential and induces procaspase-3 and PARP cleavage.2-Chlorohexadecanoic acid can across blood-brain barrier (BBB) and compromises ER- and mitochondrial functions in the human brain endothelial cell line hCMEC/D3 [1]. Uses: Scientific research. Group: Signaling pathways. CAS No. 19117-92-1. Pack Sizes: 1 mg; 5 mg; 10 mg; 25 mg. Product ID: HY-131688. |  |
| Apoptosis Activator 2 | Apoptosis activator 2 is a cell-permeable apoptosis activator that promotes the cytochrome c-dependent oligomerization of Apaf-1 into the mature apoptosome. It increases procaspase-9 processing and subsequent caspase-3 activation. It induces apoptosis in tumor cells (IC50 = 4 - 9 μM for leukemia cells) with weak or no effect on normal cell lines or those defective/deficient in Apaf-1, caspase-9 or caspase-3 activity (IC50 > 40 μM). Synonyms: Apoptosis Activator 2; AAII; N-(3,4-dichlorobenzyl) Isatin. MDK83190; MDK-83190; MDK 83190. CAS No. 79183-19-0. Molecular formula: C15H9Cl2NO2. Mole weight: 306.142. |  |
| Atractyloside, Calcium Salt | Atractyloside Calcium Salt is a specific inhibitor of the adenine nucleotide translocase (ANT), which is a mitochondrial ADP/ATP carrier. It is also a proapoptotic ligand of ANT that induces pore formation by ANT, and results in permeabilization of the mitochondria membrane. Studies on rat hearts suggest that Atractyloside inhibits chloride channels from the mitochondrial membrane. It is used to probe the source of procaspase 8 in human fibroblasts and mouse clonal striatal cells, as related to death receptor-mediated apoptosis. Atractyloside induces the release of ahyaluronidase-induced murine WW domain-containing oxidoreductase from cultured COS-7 cells, with respect to tumor necrosis factor cytotoxicity. Group: Biochemicals. Alternative Names: (2 β,15α)-15-Hydroxy-2-[[2-O-(3-methyl-1-oxobutyl)-3,4-di-O-sulfo- β-D-glucopyranosyl]oxy]-19-Norkaur-16-en-18-oic Acid Calcium Salt; 19-Norkaur-16-en-18-oic acid deriv. 1H-2,10a-Ethanophenanthrene Calcium Salt. Grades: Highly Purified. CAS No. 772298-35-8 free acid. Pack Sizes: 500ug, 1mg. US Biological Life Sciences. |  Worldwide |
| Bromoenol lactone | BEL is a selective, potent, irreversible, mechanism-based inhibitor of myocardial cytosolic calcium-independent phospholipase A2 (iPLA2) with a Ki value of 180 nM. BEL induces the proteolysis of procaspase-9 and procaspase-3 and increases cleavage of poly (ADP-ribose) polymerase. BEL also inhibits macrophage iPLA2 in a concentration-dependent manner with an IC50 value of 60 nM and is an effective enzyme-activated irreversible inhibitor of chymotrypsin Ki of 636 nM. Long term treatment with BEL increased annexin-V binding to the cell surface and nuclear DNA damage. Synonyms: BEL; Haloenol lactone; HELSS. Grades: ≥95%. CAS No. 88070-98-8. Molecular formula: C16H13BrO2. Mole weight: 317.2. | |
| caspase-1 | From mammalian monocytes. This enzyme is part of the family of inflammatory caspases, which also includes caspase-4 (EC 3.4.22.57) and caspase-5 (EC 3.4.22.58) in humans and caspase-11 (EC 3.4.22.64), caspase-12, caspase-13 and caspase-14 in mice. Contains a caspase-recruitment domain (CARD) in its N-terminal prodomain, which plays a role in procaspase activation. Cleaves pro-interleukin-1β (pro-IL-1β) to form mature IL-1β, a potent mediator of inflammation. Also activates the proinflammatory cytokine, IL-18, which is also known as interferon-γ-inducing factor. Inhibited by Ac-Tyr-Val-Ala-Asp-CHO. Caspase-11 plays a critical role in the activation of caspase-1 in mi...proteinase; ICE. Enzyme Commission Number: EC 3.4.22.36. CAS No. 122191-40-6. Storage: Store it at +4 ?C for short term. For long term storage, store it at -20 ?C?-80 ?C. Form: Liquid or lyophilized powder. EXWM-4211; caspase-1; EC 3.4.22.36; 122191-40-6; interleukin 1β-converting enzyme; protease VII; protease A; interleukin 1β precursor proteinase; interleukin 1 converting enzyme; interleukin 1β-converting endopeptidase; interleukin-1β convertase; interleukin-1β converting enzyme; interleukin-1β precursor proteinase; prointerleukin 1β protease; precursor interleukin-1β converting enzyme; pro-interleukin 1β proteinase; ICE. Cat No: EXWM-4211. |  |
| caspase-10 | Caspase-10 is an initiator caspase, as are caspase-2 (EC 3.4.22.55), caspase-8 (EC 3.4.22.61) and caspase-9 (EC 3.4.22.62). Like caspase-8, caspase-10 contains two tandem death effector domains (DEDs) in its N-terminal prodomain, and these play a role in procaspase activation. The enzyme has many overlapping substrates in common with caspase-8, such as RIP (the cleavage of which impairs NF-κB survival signalling and starts the cell-death process) and PAK2 (associated with some of the morphological features of apoptosis, such as cell rounding and apoptotic body formation). Bid, a Bcl2 protein, can be cleaved by caspase-3 (EC 3.4.22.56), caspase-8 and caspase-10 at Lys-Gln-Thr-Asp? ...u-Thr-Asp? to yield a p13 fragment that is not N-myristoylated. Belongs in peptidase family C14. Group: Enzymes. Synonyms: FLICE2, Mch4; CASP-10; ICE-like apoptotic protease 4; apoptotic protease Mch-4; FAS-associated death domain protein interleukin-1β-converting enzyme 2. Enzyme Commission Number: EC 3.4.22.63. CAS No. 189088-85-5. Storage: Store it at +4 ?C for short term. For long term storage, store it at -20 ?C?-80 ?C. Form: Liquid or lyophilized powder. EXWM-4239; caspase-10; EC 3.4.22.63; 189088-85-5; FLICE2, Mch4; CASP-10; ICE-like apoptotic protease 4; apoptotic protease Mch-4; FAS-associated death domain protein interleukin-1β-converting enzyme 2. Cat No: EXWM-4239. | |
| caspase-11 | This murine enzyme is part of the family of inflammatory caspases, which also includes caspase-1 (EC 3.4.22.36), caspase-4 (EC 3.4.22.57) and caspase-5 (EC 3.4.22.58) in humans and caspase-12, caspase-13 and caspase-14 in mice. Contains a caspase-recruitment domain (CARD) in its N-terminal prodomain, which plays a role in procaspase activation. Like caspase-5, but unlike caspase-4, this enzyme can be induced by lipopolysaccharide. This enzyme not only activates caspase-1, which is required for the maturation of proinflammatory cytokines such as interleukin-1β (IL-1β) and IL-18, but it also activates caspase-3 (EC 3.4.22.56), which leads to cellular apoptosis under pathological conditions. Belongs in peptidase family C14. Group: Enzymes. Synonyms: CASP-11. Enzyme Commission Number: EC 3.4.22.64. Storage: Store it at +4 ?C for short term. For long term storage, store it at -20 ?C?-80 ?C. Form: Liquid or lyophilized powder. EXWM-4240; caspase-11; EC 3.4.22.64; CASP-11. Cat No: EXWM-4240. | |
| caspase-2 | Caspase-2 is an initiator caspase, as are caspase-8 (EC 3.4.22.61), caspase-9 (EC 3.4.22.62) and caspase-10 (EC 3.4.22.63). Contains a caspase-recruitment domain (CARD) in its N-terminal prodomain, which plays a role in procaspase activation. Two forms of caspase-2 with antagonistic effects exist: caspase-2L induces programmed cell death and caspase-2S suppresses cell death. Caspase-2 is activated by caspase-3 (EC 3.4.22.56), or by a caspase-3-like protease. Activation involves cleavage of the N-terminal prodomain, followed by self-proteolysis between the large and small subunits of pro-caspase-2 and further proteolysis into smaller fragments. Proteolysis occurs at Asp residues and the ...s a substrate of the large isoform of pro-caspase-2 (caspase-2L) but not of the short isoform (caspase-2S). Belongs in peptidase family C14. Group: Enzymes. Synonyms: ICH-1; NEDD-2; caspase-2L; caspase-2S; neural precursor cell expressed developmentally down-regulated protein 2; CASP-2; NEDD2 protein. Enzyme Commission Number: EC 3.4.22.55. CAS No. 182372-14-1. Storage: Store it at +4 ?C for short term. For long term storage, store it at -20 ?C?-80 ?C. Form: Liquid or lyophilized powder. EXWM-4230; caspase-2; EC 3.4.22.55; 182372-14-1; ICH-1; NEDD-2; caspase-2L; caspase-2S; neural precursor cell expressed developmentally down-regulated protein 2; CASP-2; NEDD2 protein. Cat No: EXWM-4230. | |
| caspase-3 | Caspase-3 is an effector/executioner caspase, as are caspase-6 (EC 3.4.22.59) and caspase-7 (EC 3.4.22.60). These caspases are responsible for the proteolysis of the majority of cellular polypeptides [e.g. poly(ADP-ribose) polymerase (PARP)], which leads to the apoptotic phenotype. Procaspase-3 can be activated by caspase-1 (EC 3.4.22.36), caspase-8 (EC 3.4.22.61), caspase-9 (EC 3.4.22.62) and caspase-10 (EC 3.4.22.63) as well as by the serine protease granzyme B. Caspase-3 can activate procaspase-2 (EC 3.4.22.55). Activation occurs by inter-domain cleavage followed by removal of the N-terminal prodomain. Although Asp-Glu-(Val/Ile)-Asp is thought to be the preferred cleavage sequence, the enzyme can accommodate different residues at P2 and P3 of the substrate. Like caspase-2, a hydrophobic residue at P5 of caspase-3 leads to more efficient hydrolysis, e.g. (Val/Leu)-Asp-Val-Ala-Asp? is a better substrate than Asp-Val-Ala-Asp?. This is not the case for caspase-7. Belongs in peptidase family C14. Group: Enzymes. Synonyms: CPP32; apopain; yama protein. Enzyme Commission Number: EC 3.4.22.56. CAS No. 169592-56-7. Storage: Store it at +4 ?C for short term. For long term storage, store it at -20 ?C?-80 ?C. Form: Liquid or lyophilized powder. EXWM-4231; caspase-3; EC 3.4.22.56; 169592-56-7; CPP32; apopain; yama protein. Cat No: EXWM-4231. | |
| caspase-4 | This enzyme is part of the family of inflammatory caspases, which also includes caspase-1 (EC 3.4.22.36) and caspase-5 (EC 3.4.22.58) in humans and caspase-11 (EC 3.4.22.64), caspase-12, caspase-13 and caspase-14 in mice. Contains a caspase-recruitment domain (CARD) in its N-terminal prodomain, which plays a role in procaspase activation. The enzyme is able to cleave itself and the p30 caspase-1 precursor, but, unlike caspase-1, it is very inefficient at generating mature interleukin-1β (IL-1β) from pro-IL-1&beta. Both this enzyme and caspase-5 can cleave pro-caspase-3 to release the small subunit (p12) but not the large subunit (p17). The caspase-1 inhibitor Ac-Tyr-Val-Ala-Asp-CHO can also inhibit this enzyme, but more slowly. Belongs in peptidase family C14. Group: Enzymes. Synonyms: ICErelII; ICErel-II; Ich-2; transcript X; TX; TX protease; caspase 4; CASP-4. Enzyme Commission Number: EC 3.4.22.57. CAS No. 182762-08-9. Storage: Store it at +4 ?C for short term. For long term storage, store it at -20 ?C?-80 ?C. Form: Liquid or lyophilized powder. EXWM-4232; caspase-4; EC 3.4.22.57; 182762-08-9; ICErelII; ICErel-II; Ich-2; transcript X; TX; TX protease; caspase 4; CASP-4. Cat No: EXWM-4232. | |
| caspase-5 | This enzyme is part of the family of inflammatory caspases, which also includes caspase-1 (EC 3.4.22.36) and caspase-4 (EC 3.4.22.57) in humans and caspase-11 (EC 3.4.22.64), caspase-12, caspase-13 and caspase-14 in mice. Contains a caspase-recruitment domain (CARD) in its N-terminal prodomain, which plays a role in procaspase activation. The enzyme is able to cleave itself and the p30 caspase-1 precursor, but is very inefficient at generating mature interleukin-1β (IL-1β) from pro-IL-1&beta. Both this enzyme and caspase-4 can cleave pro-caspase-3 to release the small subunit (p12) but not the large subunit (p17). Unlike caspase-4, this enzyme can be induced by lipopolysaccharide. Belongs in peptidase family C14. Group: Enzymes. Synonyms: ICErel-III; Ich-3; ICH-3 protease; transcript Y; TY; CASP-5. Enzyme Commission Number: EC 3.4.22.58. CAS No. 192465-11-5. Storage: Store it at +4 ?C for short term. For long term storage, store it at -20 ?C?-80 ?C. Form: Liquid or lyophilized powder. EXWM-4233; caspase-5; EC 3.4.22.58; 192465-11-5; ICErel-III; Ich-3; ICH-3 protease; transcript Y; TY; CASP-5. Cat No: EXWM-4233. | |
| caspase-8 | Caspase-8 is an initiator caspase, as are caspase-2 (EC 3.4.22.55), caspase-9 (EC 3.4.22.62) and caspase-10 (EC 3.4.22.63). Caspase-8 is the apical activator of the extrinsic (death receptor) apoptosis pathway, triggered by death receptor ligation. It contains two tandem death effector domains (DEDs) in its N-terminal prodomain, and these play a role in procaspase activation. This enzyme is linked to cell surface death receptors such as Fas. When Fas is aggregated by the Fas ligand, procaspase-8 is recruited to the death receptor where it is activated. The enzyme has a preference for Glu at P3 and prefers small residues, such as Gly, Ser and Ala, at the P1' position. It has very broad P...ORT1-associated CED-3 homolog; Mch5; mammalian Ced-3 homolog 5; CASP-8; ICE-like apoptotic protease 5; FADD-homologous ICE/CED-3-like protease; apoptotic cysteine protease; apoptotic protease Mch-5; CAP4. Enzyme Commission Number: EC 3.4.22.61. CAS No. 179241-78-2. Storage: Store it at +4 ?C for short term. For long term storage, store it at -20 ?C?-80 ?C. Form: Liquid or lyophilized powder. EXWM-4237; caspase-8; EC 3.4.22.61; 179241-78-2; FLICE, FADD-like ICE; MACH; MORT1-associated CED-3 homolog; Mch5; mammalian Ced-3 homolog 5; CASP-8; ICE-like apoptotic protease 5; FADD-homologous ICE/CED-3-like protease; apoptotic cysteine protease; apoptotic protease Mch-5; CAP4. Cat No: EXWM-4237. | |
| caspase-9 | Caspase-9 is an initiator caspase, as are caspase -2 (EC 3.4.22.55), caspase-8 (EC 3.4.22.61) and caspase-10 (EC 3.4.22.63). Caspase-9 contains a caspase-recruitment domain (CARD) in its N-terminal prodomain, which plays a role in procaspase activation. An alternatively spliced version of caspase-9 also exists, caspase-9S, that inhibits apoptosis, similar to the situation found with caspase-2. Phosphorylation of caspase-9 from some species by Akt, a serine-threonine protein kinase, inhibits caspase activity in vitro and caspase activation in vivo. The activity of caspase-9 is increased dramatically upon association with the apoptosome but the enzyme can be activated without proteolytic cleavage. Procaspase-3 is the enzyme's physiological substrate. Belongs in peptidase family C14. Group: Enzymes. Synonyms: CASP-9; ICE-like apoptotic protease 6; ICE-LAP6; apoptotic protease Mch-6; apoptotic protease-activating factor 3; APAF-3. Enzyme Commission Number: EC 3.4.22.62. CAS No. 180189-96-2. Storage: Store it at +4 ?C for short term. For long term storage, store it at -20 ?C?-80 ?C. Form: Liquid or lyophilized powder. EXWM-4238; caspase-9; EC 3.4.22.62; 180189-96-2; CASP-9; ICE-like apoptotic protease 6; ICE-LAP6; apoptotic protease Mch-6; apoptotic protease-activating factor 3; APAF-3. Cat No: EXWM-4238. | |
| Diethylnorspermine | diethylnorspermine, also known as DENSPM, is a potent inducer of spermidine/spermine N1-acetyltransferase, is able to increase enzyme activity 200-1000 fold. The cell death induced by DENSPM treatment was apoptotic, as evidenced by cleavage of procaspase 3 and induction of caspase-3 activity. The DENSPM-induced polyamine depletion was also caused by the inhibition of ornithine decarboxylase. LA-N-1 cells contained a higher level of the prosurvival protein survivin, which was further increased after DENSPM treatment. Synonyms: DE-333, DE 333; DE333; BE-333, BE 333; BE333; N1,N11-Diethylnorspermine; 1,11-bis(ethylamino)-4,8-diazaundecan. CAS No. 121749-39-1. Molecular formula: C13H36Cl4N4. Mole weight: 244.42. | |
| Imiquimod | Cell-permeable. Topical immune response modifier that displays anti-angiogenic, anti-viral and anti-inflammatory properties. Up-regulates IL-18 and down-regulates MMP-9 through recognition of Toll-like receptor 7 (TLR7) and subsequent activation of MyD88-dependent pathway. Stimulates proinflammatory cytokine production interferon-alpha (IFN-alpha), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) and activates NF-kappaB. Caspase-3 activator that directly induces procaspase-3 cleavage. Anti-cancer compound. Apoptosis inducer. Antiproliferative, independent of immune system activation or function. Approved treatment for external genital warts caused by human papillomavirus infection. Group: Biochemicals. Alternative Names: 1-(2-Methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine; R-837; S-26308. Grades: Highly Purified. CAS No. 99011-02-6. Pack Sizes: 100mg, 250mg, 500mg, 1g. Molecular Formula: C14H16N4. US Biological Life Sciences. | Worldwide |
| Native Bovine Cathepsin B | Cathepsin B has been found to cleave procaspase 1 and procaspase 11 and to induce apoptosis in digitonin-permeabilized cells. Translocation of cathepsin B from the cytoplasm to the nucleus contributes to bile salt induced apoptosis of Rat hepatocytes. Levels of cathepsin B in PC12 cells significantly decrease 12 to 24 hours after apoptosis is induced. Group: Enzymes. Synonyms: CTSB; cathepsin B; 9047-22-7; APPS; CPSB; cathepsin B1 (obsolete); cathepsin II. CAS No. 9047-22-7. Cathepsin B. Activity: > 10 units/mg protein. Form: Lyophilized powder containing sodium phosphate, sodium chloride and ~6% EDTA as stabilizer. Source: Bovine spleen. Species: Bovine. CTSB; cathepsin B; 9047-22-7; APPS; CPSB; cathepsin B1 (obsolete); cathepsin II. Cat No: NATE-0167. | |
| Native Human Cathepsin B | Cathepsin B has been found to cleave procaspase 1 and procaspase 11 and to induce apoptosis in digitonin-permeabilized cells. Translocation of cathepsin B from the cytoplasm to the nucleus contributes to bile salt induced apoptosis of rat hepatocytes. Levels of cathepsin B in PC12 cells significantly decrease 12 to 24 hours after apoptosis is induced. Group: Enzymes. Synonyms: CTSB; cathepsin B; cathepsin B1; APPS; CPSB; EC 3.4.22.1; 9047-22-7; cathepsin II; CatB. Enzyme Commission Number: EC 3.4.22.1. CAS No. 9047-22-7. Cathepsin B. Activity: > 2 ,000 units/mg protein (E1%/280). Storage: -20°C. Form: buffered aqueous solution. Solution in 50 mM sodium acetate, pH 5.0, with 1 mM EDTA. Source: Human liver. Species: Human. CTSB; cathepsin B; cathepsin B1; APPS; CPSB; EC 3.4.22.1; 9047-22-7; cathepsin II; CatB. Cat No: NATE-0168. | |
| N- (Ethoxycarbonylmethyl) piperazine | N- (Ethoxycarbonylmethyl) piperazine is used in the preparation of aralkylpiperazine- and aryl-substituted hydrazines, particularly benzylpiperazineacetyl hydrazones of hydroxyaryl aldehydes, as selective inducers of apoptosis and activators of procaspases for use as anticancer agents. Group: Biochemicals. Alternative Names: 1-Piperazineacetic Acid Ethyl Ester; 2-(Piperazin-1-yl)acetic Acid Ethyl Ester; 4- (Carboethoxymethyl) piperazine; Ethyl 1-piperazineacetate; Ethyl 1-Piperazinylacetate; Ethyl 2-(piperazin-1-yl)acetate; Ethyl 2-Piperazinoacetate; Ethyl Piperazinoacetate; N- (Carboethoxymethyl) piperazine; N- (Ethoxycarbonylmethyl) piperazine; Piperazin-1-ylacetic Acid Ethyl Ester. Grades: Highly Purified. CAS No. 40004-08-8. Pack Sizes: 100mg. US Biological Life Sciences. | Worldwide |
| PAC-1 | PAC-1 is a procaspase-3 activator that induces apoptosis in cancer cells with an EC 50 of 2.08 μM. Uses: Scientific research. Group: Signaling pathways. Alternative Names: Procaspase activating compound 1. CAS No. 315183-21-2. Pack Sizes: 10 mM * 1 mL; 5 mg; 10 mg; 50 mg; 100 mg; 500 mg. Product ID: HY-13523. | |
| PAC-1 | PAC-1 is known as the first procaspase activating compound, which selectively induces apoptosis, or cell suicide, in cancerous cells. PAC-1 has shown good results in mouse models and is being further evaluated for use in humans. In 2010 a published study showed PAC-1 to be safe to research dogs, and a second study published later that same year reported that a PAC-1 derivative (called S-PAC-1) was well tolerated in a small Phase I Clinical Trial of pet dogs with lymphoma. Even at low doses of S-PAC-1, tumors regressed in 1/6 dogs, and the disease was stabilized (no additional tumor growth) in 3/6 dogs. Synonyms: 1-Piperazineacetic acid, 4-(phenylmethyl)-, 2-[[2-hydroxy-3-(2-propen-1-yl)phenyl]methylene]hydrazide; 1-Piperazineacetic acid, 4-(phenylmethyl)-, [[2-hydroxy-3-(2-propenyl)phenyl]methylene]hydrazide; PAC 1; PAC1; Procaspase activating compound 1. Grades: >98%. CAS No. 315183-21-2. Molecular formula: C23H28N4O2. Mole weight: 392.49. | |
| RO-3306 | Selective CDK 1 inhibitor (Cdk1/B1 and Cdk1/A). Potential anti-cancer compound. Cell cycle arrest inducer at G1, S and G2/M. Apoptosis inducer in embryonic stem cells. Actively enhances downstream p53 signaling to promote apoptosis in AML cell lines. Suppresses phosphorylation of p53 at Ser315 and procaspase-8 at Ser387. Enhances Fas-mediated activation and processing of procaspase-8 in mitotic cells towards. Group: Biochemicals. Alternative Names: (5Z)-2-((Thiophen-2-yl)methylamino)-5-((quinolin-6-yl)methylene)thiazol-4(5H)-one. Grades: Highly Purified. CAS No. 872573-93-8. Pack Sizes: 1mg, 5mg. Molecular Formula: C??H??N?OS?. US Biological Life Sciences. | Worldwide |
| RO-3306, CDK 1 Inhibitor ((5Z)-2-((Thiophen-2-yl)methylamino)-5-((quinolin-6-yl)methylene)thiazol-4(5H)-one) | Cell-permeable. A selective CDK 1 inhibitor (Cdk1/B1 and Cdk1/A). Arrests cell cycle at G1, S, and G2/M and induces apoptosis in embryonic stem cells. Actively enhances downstream p53 signaling to promote apoptosis in AML cell lines, and suppresses phosphorylation of p53 at Ser315 and procaspase-8 at Ser387. Group: Biochemicals. Grades: Highly Purified. CAS No. 872573-93-8. Pack Sizes: 1mg, 5mg. US Biological Life Sciences. | Worldwide |
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