PY-60
目录号 : GC62424
PY-60 是一种靶向膜联蛋白A2 (ANXA2) 的 YAP 转录活性的特异的激活剂 (Kd=1.4 µM)。PY-60 直接与 ANXA2 结合并拮抗其抑制 YAP 活性的正常细胞功能。
Cas No.:2765218-56-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
PY-60 is a robust and specific activator of YAP transcriptional activity that targets annexin A2 (ANXA2) with a Kd of 1.4 µM. PY-60 directly binds to ANXA2 and antagonizes its normal cellular function of repressing YAP activity[1].
PY-60 targets ANXA2 to activate YAP[1].PY-60, a thiazole-substituted derivative, dose-dependently induces luciferase activity in 293A-TEAD-LUC cells in the presence or absence of serum when cells were plated at high cell density (EC50= 1.5 and 1.6 µM, respectively). PY-60 treatment also dose-dependently promoted the association of YAP and TEAD proteins in cells and induced the nuclear localization of YAP in response to increased cell density. PY-60 robustly increases the levels of YAP-controlled transcripts (that is, ANRKD1, CYR61 and CTGF) in 293A cells and other human cell lines (that is, MCF10A, HEK293T, H69 and HaCaT), but did not augment the levels of YAP itself (YAP1)[1]. PY-60 activates a proproliferative, YAP-dependent transcriptional program in the adult animal capable of remodeling the epidermis through proliferation[1]. PY-60 liberates the ANXA2-YAP complex from the cell membrane and competes for ANXA2 binding of phosphoinositides[1].
PY-60 (10 uM; applied topically to the dorsal skin of wild-type adult C57BL/6 mice over the course of 10 days) promotes a dramatic expansion of keratinocytes and K14-positive precursors, as assessed by hematoxylin and eosin and anti-K14 histological staining at the study end. PY-60 results in an approximate doubling of epidermal thickness, a result derived from an increased number of keratinocytes per unit length of skin[1].
[1]. Shalhout SZ, et al. YAP-dependent proliferation by a small molecule targeting annexin A2. Nat Chem Biol. 2021;17(7):767-775.
| Cas No. | 2765218-56-0 | SDF | |
| 分子式 | C16H15N3O2S | 分子量 | 313.37 |
| 溶解度 | DMSO : 100 mg/mL (319.11 mM; Need ultrasonic) | 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 | 3.1911 mL | 15.9556 mL | 31.9112 mL |
| 5 mM | 0.6382 mL | 3.1911 mL | 6.3822 mL |
| 10 mM | 0.3191 mL | 1.5956 mL | 3.1911 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。
YAP-dependent proliferation by a small molecule targeting annexin A2
Nat Chem Biol 2021 Jul;17(7):767-775.PMID:33723431DOI:10.1038/s41589-021-00755-0.
The transcriptional coactivator Yes-associated protein 1 (YAP) orchestrates a proproliferative transcriptional program that controls the fate of somatic stem cells and the regenerative responses of certain tissues. As such, agents that activate YAP may hold therapeutic potential in disease states exacerbated by insufficient proliferative repair. Here we report the discovery of a small molecule, termed PY-60, which robustly activates YAP transcriptional activity in vitro and promotes YAP-dependent expansion of epidermal keratinocytes in mouse following topical drug administration. Chemical proteomics revealed the relevant target of PY-60 to be annexin A2 (ANXA2), a protein that directly associates with YAP at the cell membrane in response to increased cell density. PY-60 treatment liberates ANXA2 from the membrane, ultimately promoting a phosphatase-bound, nonphosphorylated and transcriptionally active form of YAP. This work reveals ANXA2 as a previously undescribed, druggable component of the Hippo pathway and suggests a mechanistic rationale to promote regenerative repair in disease.
Effect of cell density on the malignant biological behavior of breast cancer by altering the subcellular localization of ANXA2 and its clinical implications
Clin Transl Oncol 2022 Nov;24(11):2136-2145.PMID:35778647DOI:10.1007/s12094-022-02865-0.
Objective: To investigate the subcellular localization of ANXA2 in breast cancer of different cell densities in humans and its relationship with the clinicopathological features of patients. To investigate the differences in ANXA2 subcellular localization in MDA-MB-231 cells of different cell densities. To compare the proliferation, invasion, and migration ability of MDA-MB-231 cells under different ANXA2 subcellular localization. Methods: Immunohistochemistry was applied to detect the subcellular localization of ANXA2 in tissue sections of 60 breast cancer patients, and the association with ANXA2 subcellular localization was verified in conjunction with cell density. To investigate the relationship between cell density and clinicopathological data of breast cancer patients. To establish high- and low-density models of MDA-MB-231 breast cancer cell lines and verify the subcellular localization of ANXA2 using immunofluorescence and observation under confocal microscopy. The proliferation, migration, and invasion ability of MDA-MB-231 cells under different subcellular localization of ANXA2 were detected and compared using CCK-8 assay and Transwell assay. After changing the subcellular localization of ANXA2 in high-density MDA-MB-231 cells with PY-60, changes in biological behaviors of the compared MDA-MB-231 cells were observed. Two different 4T1 cell lines with high and low densities were implanted subcutaneously in nude mice to observe the effects of different cell densities on tumor growth in nude mice. Results: The clinical data showed that breast cancer with high cell density had higher T stage and higher TNM stage, and the cell density was positively correlated with breast cancer mass size. ANXA2 was mainly localized to the cell membrane when the cell density of breast cancer cells was high and to the cytoplasm when the cell density was low. The CCK-8 assay showed that the proliferation rate of MDA-MB-231 cells increased (P < 0.05) after shifting the subcellular localization of ANXA2 from the cell membrane to the cytoplasm. Transwell invasion assay and Transwell migration assay showed that the invasion and migration ability of MDA-MB-231 cells increased significantly after the subcellular localization of ANXA2 was transferred from the cell membrane to the cytoplasm (P < 0.05). The animal experiments showed that high-density breast cancer cells could promote the growth of subcutaneous tumors in nude mice relative to low-density breast cancer cells. Conclusion: Cell density can regulate the subcellular localization of ANXA2, and changes in the subcellular localization of ANXA2 are accompanied by the changes in the biological behavior of breast cancer.
Feasibility of spherical aberration correction with aspheric intraocular lenses in cataract surgery based on individual pupil diameter
J Cataract Refract Surg 2009 Oct;35(10):1725-33.PMID:19781467DOI:10.1016/j.jcrs.2009.05.031.
Purpose: To evaluate the feasibility of correcting spherical aberration with aspheric intraocular lenses (IOLs) in cataract surgery based on individual pupil diameter. Setting: Keio University Hospital, Tokyo, Japan. Methods: In this prospective study, eyes having cataract surgery were divided into 4 groups based on IOL type: aspheric SN (AcrySof SN60WF), aspheric ZA (Tecnis ZA9003), aspheric PY (Hoya PY-60 AD), and spherical (AcrySof Natural SN60AT). Postoperative higher-order aberrations (HOAs) of the cornea and whole eye and the pupil diameter under photopic and mesopic conditions were measured. The HOA was calculated using the individual pupil diameter. The correlation between corneal and ocular spherical aberrations and pupil diameter was evaluated. Results: Each group comprised 30 eyes. Ocular spherical aberrations were significantly lower than corneal spherical aberrations under mesopic conditions in the aspheric SN group, the aspheric ZA group, and the aspheric PY group (P<.05); there was no significant difference between the aberrations in the spherical group. Linear regression showed significant correlations between postoperative corneal and ocular spherical aberrations (beta = 0.39, aspheric SN; beta = 0.38, aspheric ZA; beta = 0.58, aspheric PY; beta = 0.79, spherical). The differences in corneal and ocular spherical aberrations were significantly correlated with pupil diameter in the aspheric IOL groups but not in the spherical IOL group. Conclusions: The amount of spherical aberration correction by aspheric IOLs varied depending on IOL type and individual pupil diameter. The linear regression equation in this study may make it possible to customize postoperative ocular spherical aberration after cataract surgery.
[Evaluation of post intraocular lens implantation detrition of clear corneal incisions using an injector system in porcine eyes]
Nippon Ganka Gakkai Zasshi 2010 May;114(5):429-35.PMID:20545216doi
Purpose: To evaluate the detrition of clear corneal incisions (CCIs) after intraocular lens (IOL) implantation using an injector system in porcine eyes. Methods: Group A: after CCIs were performed with 1.8, 2.0, 2.2, 2.4, and 2.65 mm wide slit knives, a Y-60 H (HOYA) IOL was implanted in the anterior chamber using an injector system. Group B: after CCIs were performed with 2.4, 2.65, 2.8, 3.0, and 3.2 mm wide slit knives, a PY-60 R (HOYA) IOL was implanted in the anterior chamber using an injector system. Group C: after CCIs were performed with 2.8, 3.0, 3.2, 3.4 mm wide slit knives, a SN 60 AT (Alcon) IOL was implanted in the anterior chamber using an injector system. Control: CCIs were performed with 3.0 mm wide slit knives. Each group used five porcine eyes for each slit knife (Group A 25 eyes; Group B 25 eyes; Group C 20 eyes; CONTROL 5 eyes). The detrition of the CCIs was evaluated on three different aspects using a scanning electron microscope: a) external expansion at both edges of CCIs; b) rupture of the collagen fibers; c) expansion between the collagen fibers. Aspects a, b and c were given a score of 0, 1, and 2, respectively, and the total points were compared statistically between test and control groups. Results: The degree of CCIs detrition was significantly reduced in CCIs with a width of more than 2.4 mm of CCIs width in Group A, more than 3.0 mm in Group B, and more than 3.2 mm in Group C. Conclusions: Minimizing the detrition of corneal incisions after IOL implantation needs a larger than the recommended width of corneal incision.