CP-10
目录号 : GC35739
CP-10 是具有高选择性，特异性和显著的 CDK6 降解潜力 (DC50=2.1 nM) 的 PROTAC。它抑制几种造血细胞癌的增殖，包括多发性骨髓瘤，并且对突变和过表达的 CDK6 仍然可以降解。
Cas No.:2366268-80-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
CP-10 is a PROTAC with highly selective, specific, and remarkable CDK6 degradation (DC50=2.1 nM). It inhibits proliferation of several haematopoietic cancer cells with impressive potency including multiple myeloma, and can still degrades mutated and overexpressed CDK6[1]. CDK6|2.1 nM (DC50)
CP-10 induces nearly 72% degradation of CDK6 at 10 nM and 89% at 100 nM in human glioblastoma U251 cells. The degradation of CDK4 induced by CP-10 is far weaker than that of CDK6 (DC50: 50-80 fold)[1].CP-10 displays a cell inhibition potential in multiple myeloma cell MM.1S (IC50≈10 nM) and mantle cell lymphoma cells (in Mino, IC50≈8 nM)[1].
[1]. Su S, et al. Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders. J Med Chem. 2019 Aug 2.
| Cas No. | 2366268-80-4 | SDF | |
| Canonical SMILES | CC(C(C1=O)=C(C)C2=CN=C(NC3=CC=C(N4CCN(CC5=CN(CCOCCNC6=CC=CC(C(N7C8CCC(NC8=O)=O)=O)=C6C7=O)N=N5)CC4)C=N3)N=C2N1C9CCCC9)=O | ||
| 分子式 | C44H49N13O7 | 分子量 | 871.94 |
| 溶解度 | DMSO: 200 mg/mL (229.37 mM) | 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 | 1.1469 mL | 5.7343 mL | 11.4687 mL |
| 5 mM | 0.2294 mL | 1.1469 mL | 2.2937 mL |
| 10 mM | 0.1147 mL | 0.5734 mL | 1.1469 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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。
CP-10, a chemotactic peptide, is expressed in lesions of experimental autoimmune encephalomyelitis, neuritis, uveitis and in C6 gliomas
J Neuroimmunol 1999 Jan 1;93(1-2):156-63.PMID:10378879DOI:10.1016/s0165-5728(98)00221-5.
CP-10 (chemotactic protein of m.w. 10,000) is a member of the S100 superfamily of Ca2+ binding peptides, which has potent chemotactic activity for murine and human myeloid cells. Here we report on the generation of monoclonal antibodies against CP-10 and accumulation of CP-10+ cells during experimental autoimmune encephalomyelitis (EAE), neuritis (EAN), uveitis (EAU) and in experimentally transplanted C6 gliomas. During acute inflammation, CP-10 is mainly expressed by large ED1+ monocytic perivascular cells that accumulate at days 11-14. CP-10+ cells are predominantly located in areas of cellular infiltration but are as well found in the meninges and infiltrating the brain parenchyma. In transplanted gliomas, CP-10+ cells are located exclusively within the tumor parenchyma. Using double labeling experiments, other cells participating in the inflammatory reaction were found to express CP-10, like few lymphoblastic W3/13+ cells in the vicinity of the inflammatory infiltrate.
Induction of the chemotactic S100 protein, CP-10, in monocyte/macrophages by lipopolysaccharide
Blood 1996 May 1;87(9):3919-28.PMID:8611721doi
The murine S100 protein CP-10 is a potent chemotactic factor for murine and human myeloid cells in vivo and in vitro. This is the first report describing regulations of the CP-10 gene by a proinflammatory stimulus, lipopolysaccharide (LPS), in cells of the monocyte/macrophage lineage. Murine monocyte/macrophage-like WEHI 265 and RAW 264.7 cells preexposed to 5 to 50 ng/mL LPS expressed significant levels of CP-10 mRNA 4 hours, and maximal at 20 hours, after a secondary LPS challenge. This was accompanied by increasing levels of cell-associated and released CP-10 protein. In contrast, a single dose of LPS upregulated CP-10 mRNA in elicited peritoneal macrophages, whereas mRNA and protein levels decreased following LPS challenge. The state of macrophage differentiation may control responsiveness as LPS had no effect on CP-10 basal levels in bone marrow derived macrophages. LPS-induced CP-10 expression was controlled at the transcriptional level and nuclear run-on and protein synthesis inhibition assays indicated that LPS priming and challenge of RAW cells occurred via distinct pathways. MRP14, another S100 protein generally coordinately expressed with human MRP8, was not induced by LPS under the same conditions. We propose that CP-10 may play a key role in recruitment of leukocytes into tissues in response to gram-negative bacterial infection.
S100 protein CP-10 stimulates myeloid cell chemotaxis without activation
J Cell Physiol 1996 Feb;166(2):427-37.PMID:8592003DOI:10.1002/(SICI)1097-4652(199602)166:2<427::AID-JCP21>3.0.CO;2-6.
Leukocyte recruitment to inflammatory foci is generally associated with cellular activation. Recent evidence suggests that chemotactic agents can be divided into two classes, "classical chemoattractants" such as FMLP, C5a, and IL-8, which stimulate directed migration and activation events and "pure chemoattractants" such as TGF-beta 1 which influence actin polymerisation and movement but not oxidative burst and associated granular enzyme release. The studies reported here demonstrate that the murine S100 chemoattractant protein, CP-10, belongs to the "non-classical" group. Despite its potent chemotactic activity for neutrophils and monocytes/macrophages, CP-10 failed to increase [Ca2+]i in human or mouse PMN, although chemotaxis was inhibited by pertussis toxin, confirming the suggestion of a novel Ca(2+)-independent G-protein-coupled pathway for post-receptor signal transduction triggered by "pure chemoattractants." The co-ordinated up-regulation of Mac-1 and down-regulation of L-selectin induced by FMLP on human PMN in vitro was not observed with CP-10. Quantitative changes in immediate (30 s) actin polymerisation occurred with FMLP and CP-10-treated human PMN. The relative F-actin increases induced in WEHI 265 monocytoid cells by FMLP and CP-10 was optimal at 60 s and declined over 120 s. F-actin changes reflected the concentration and potencies of the agonists required to provoke chemotaxis. After 90 min, CP-10 profoundly altered cell shape and increased both cell size and F-actin within pseudopodia. These changes are typical of those mediating leukocyte deformability, and CP-10 may mediate leukocyte retention within microcapillaries and thereby contribute to the initiation of inflammation in vascular beds.
Acute inflammatory activity of the S100 protein CP-10. Activation of neutrophils in vivo and in vitro
J Immunol 1994 Feb 15;152(4):1888-97.PMID:8120396doi
The murine S100 chemotactic protein of m.w. 10,000 termed (CP-10), has potent chemotactic activity for murine and human myeloid cells. We examined the ability of a synthetic CP-10 hinge region peptide CP-10(42-55) and rCP-10 to act as chemotactic agents and induce expression of the adhesion molecule Mac-1 (CD 11b/CD 18) in vivo. Maximal neutrophil (PMN) accumulation occurred between 2 to 8 h after mouse footpad injection of rCP-10 (10(-7) M) or CP-10 peptide (10(-6) M). The infiltrating PMN expressed high levels of Mac-1, and low levels of the murine L-selectin Mel-14. Injection of CP-10 peptide i.p. also induced infiltration of PMNs that expressed high levels of Mac-1. Cell suspensions obtained after i.p. injection of CP-10 peptide could be significantly inhibited from adhering to fibrinogen-coated plates when incubated with anti-Mac-1 antibody. The chemotactic activity of CP-10 peptide toward murine inflammatory PMN in vitro was also inhibited by anti-Mac-1 antibody. Neither CP-10 analogue stimulated or primed murine inflammatory or human blood neutrophils for superoxide production or granular enzyme release. The localization of CP-10 in vivo was examined using murine footpads injected with LPS and was found to be concentrated around the endothelial cells of the small blood vessels. This distribution suggests that the accumulated CP-10 the may contribute to the generation of a chemotactic gradient.
Recombinant and cellular expression of the murine chemotactic protein, CP-10
DNA Cell Biol 1994 Feb;13(2):183-92.PMID:8179823DOI:10.1089/dna.1994.13.183.
The S100 protein CP-10 (chemotactic protein, 10 kD), a potent chemotactic factor for murine and human polymorphonuclear cells (PMN) and murine monocytes, has been purified in small amounts from supernatants of activated murine spleen cells (Lackmann et al., 1992). To obtain a more abundant source of the protein, CP-10 was expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST). The property of S100 proteins to undergo calcium-dependent conformational changes was used in a novel approach to optimize the release of recombinant (r) CP-10 by thrombin cleavage. Purified rCP-10 was characterized by amino-terminal sequence analysis and bioassays. Optimal chemotactic activity of rCP-10 for murine PMN and WEHI-265 monocytoid cells was 10(-11) M (native protein has optimal chemotactic activity between 10(-11) and 10(-13) M). Immunization of rabbits with the GST/CP-10 fusion protein bound to glutathione-agarose beads resulted in high titer, specific antibodies that neutralized CP-10-initiated chemotaxis and were suitable for immunoblotting. A combination of Western and Northern analyses identified CP-10 in murine peritoneal exudate PMN and macrophages, splenocytes, bone marrow cells, and WEHI-265 cells (all of myeloid origin), but not in thymus, liver, lung, 3T3 fibroblasts, EL4 lymphoma cells, or bEND 3 brain endothelial cells, indicating cell-specific regulation of CP-10 expression.