Copanlisib (BAY 80-6946)

別名: BAY 80-6946

目錄號(hào)：S2802 Purity: 99.97%

Copanlisib是一個(gè)高效的泛I型 PI3K抑制劑，其對(duì)PI3Kα/β/γ/δ抑制的IC50分別為0.5, 3.7, 6.4, and 0.7 nM。Phase 3。此產(chǎn)品溶解度不佳，動(dòng)物實(shí)驗(yàn)可用，細(xì)胞實(shí)驗(yàn)請(qǐng)謹(jǐn)慎選擇！

Copanlisib (BAY 80-6946) Chemical Structure

CAS: 1032568-63-0

規(guī)格	價(jià)格	庫(kù)存
1mg	1040.13	現(xiàn)貨
5mg	1122.03	現(xiàn)貨
10mg	1793.61	現(xiàn)貨
50mg	7944.3	現(xiàn)貨
1g	33554.43	現(xiàn)貨
更大包裝有超大折扣
400-668-6834 [email protected]

產(chǎn)品質(zhì)控

批次：純度： 99.97%

99.97

常與Copanlisib (BAY 80-6946)一起在實(shí)驗(yàn)中被使用的化合物

Darolutamide (ODM-201)

Copanlisib和Darolutamide通過強(qiáng)烈誘導(dǎo)細(xì)胞凋亡和防止促凋亡基因下調(diào)，抑制體外前列腺癌模型的增殖。

Tazemetostat (EPZ-6438)

Copanlisib和Tazemetostat聯(lián)合使用可在Calu3、Sw1573和所有BEAS2B細(xì)胞系中誘導(dǎo)較高的PIK3IP1表達(dá)。

Anetumab ravtansine

Copanlisib和Anetumab ravtansine組合顯示體外OVCAR-3和OVCAR-8細(xì)胞系細(xì)胞凋亡增加。

Venetoclax (ABT-199)

Copanlisib聯(lián)合Venetoclax可通過下調(diào)BCL-XL/MCL1基因誘導(dǎo)MCL和MZL細(xì)胞凋亡。

Abemaciclib

Copanlisib和Abemaciclib聯(lián)合療法可有效克服venetoclax耐藥性，成為未來(lái)難治性/復(fù)發(fā)患者的有效治療方案。

Copanlisib (BAY 80-6946)相關(guān)產(chǎn)品

相關(guān)靶點(diǎn)	p110α p110β p110δ p110γ C2β Vps34	點(diǎn)擊展開
相關(guān)產(chǎn)品	LY294002 3-Methyladenine (3-MA) Dactolisib (BEZ235) Pictilisib (GDC-0941) Wortmannin (SL-2052) Buparlisib (BKM120) PI-103 TGX-221 ZSTK474 Omipalisib (GSK2126458) A66 PF-04691502 PIK-75 HCl IC-87114 740 Y-P (PDGFR 740Y-P) AS-605240 Taselisib (GDC 0032) Apitolisib (GDC-0980) SAR405 VPS34-IN1 PIK-90 AZD6482 Gedatolisib (PKI-587) AS-252424 HS-173 Eganelisib (IPI-549) VS-5584 (SB2343) GSK2636771 AZD8186 GSK1059615 Pilaralisib (XL147) TG100-115 CZC24832 Voxtalisib (XL765) XL147 analogue AS-604850 BGT226 (NVP-BGT226) maleate Quercetin Dihydrate Samotolisib (LY3023414) VPS34 inhibitor 1 (Compound 19) Voxtalisib (XL765) Analogue AMG319 Nemiralisib GO-203 TFA CH5132799 PKI-402 Bimiralisib (PQR309) TG100713 Paxalisib (GDC-0084) SF2523 Serabelisib (TAK-117) PIK-294 PI-3065 GNE-317 AZD8835 GDC-0326 Inavolisib (GDC-0077) Gallein PF-4989216 CAY10505 (E)-Akt inhibitor-IV Seletalisib (UCB-5857) leniolisib (CDZ 173) Selective PI3Kδ Inhibitor 1 (compound 7n) GNE-477 GNE-493	點(diǎn)擊展開
相關(guān)化合物庫(kù)	激酶抑制劑庫(kù) PI3K/Akt 抑制劑庫(kù) 凋亡分子化合物庫(kù) 細(xì)胞周期化合物庫(kù) NF-κB信號(hào)通路庫(kù)	點(diǎn)擊展開

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系	實(shí)驗(yàn)類型	給藥濃度	孵育時(shí)間	活性描述	文獻(xiàn)信息(PMID)
BT-474	Function assay	50 nM	0.5, 2, 4, 8, 24 h	rapidly inhibits the phosphorylation of AKT (S473, T308) as well as its direct substrates PRAS40 (T246) and GSK3β (S9), and inhibition was sustained for up to 24 hours	24436048
HepG2	Growth inhibiton assay	100 nM		Copanlisib dose-dependently inhibited cell growth in vitro. IC50=31.6 nM.	30962952
Huh7	Growth inhibiton assay	100 nM		Copanlisib dose-dependently inhibited cell growth in vitro. IC50=47.9 nM.	30962952
MCF-7	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
BT-20	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
MDA-MB-361	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
MDA-MB-453	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
HCC-1954	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
UACC-893	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
SK-BR-3	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
JVM-3	Function assay		48 h	inhibits metabolic activity with an IC50 of 2 μM in the XTT assay	25912635
T-47D	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
HCC1806	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
NCI-H292	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
NCI-H1650	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
CCRF-SB	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
U937	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
SU-DHL-4	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
SU-DHL-5	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
HCT116	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
A549 cells	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
SK-MEL-30	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
SK-MEL-2 cells	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
NCI-H1703	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
NCI-H661	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
PC9	Function assay		0, 1, 2, 4 h	downregulation of P-AKT	24436048
Chang	Growth inhibiton assay			IC50=442 nM	30962952
PLCPRF5	Growth inhibiton assay			IC50=283 nM	30962952
Hep3B	Growth inhibiton assay			IC50=72.4 nM	30962952
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
點(diǎn)擊查看更多細(xì)胞系數(shù)據(jù)

生物活性

產(chǎn)品描述

靶點(diǎn)

PI3Kα ^[1] (Cell-free assay)	PI3Kδ ^[1] (Cell-free assay)	PI3Kβ ^[1] (Cell-free assay)	PI3Kγ ^[1] (Cell-free assay)
0.5 nM	0.7 nM	3.7 nM	6.4 nM

體外研究(In Vitro)
體外研究活性	BAY 80-6946是PI3K抑制劑，具有抗腫瘤活性。BAY 86-9766抑制HuCCT-1 (KRAS^G12D) 和EGI-1 (KRAS^G12D) 細(xì)胞系增殖，IC50分別為147 nM 和137 nM。^[2]
激酶實(shí)驗(yàn)	PI3Kα和PI3Kβ放射性脂質(zhì)激酶檢測(cè)
激酶實(shí)驗(yàn)	p110α生化檢測(cè)是一種放射性測(cè)定，測(cè)量³³P滲透進(jìn)p110α底物磷脂酰肌醇（PI）的程度。His標(biāo)記的N-末端截短的(ΔN 1-108) p110α和同樣截短的缺乏p85結(jié)合域的p110β(ΔN 1-108) 蛋白在Sf9細(xì)胞中表達(dá)，且純化到50%以上純度。為了獲得 IC50值,使用 MaxiSorp 板在以下條件下在384孔板中進(jìn)行反應(yīng)。每孔使用2 μg在氯仿稀釋的摩爾比為1:1的磷脂酰肌醇（PI）和磷脂酰絲氨酸（PS）包被實(shí)驗(yàn)板。將實(shí)驗(yàn)板置于通風(fēng)櫥中過夜，蒸發(fā)有機(jī)溶液。將實(shí)驗(yàn)板密封在4°C貯存1個(gè)月。每孔加入7.5 ng截短的p110α蛋白，每孔中含9 μL 實(shí)驗(yàn) buffer (50mM MOPSO pH 7.0,100 mM NaCl, 4mM MgCl₂, 0.1%(w/v)BSA)，除了對(duì)照組只含實(shí)驗(yàn) buffer。1μL 溶于DMSO的實(shí)驗(yàn)化合物從稀釋液中轉(zhuǎn)移，獲得8點(diǎn)劑量反應(yīng) (0.0, 0.003, 0.01, 0.03, 0.1, 0.3, 1.0, 3.0 和 10 μM 終濃度BAY化合物)。加入含 20 μCi/mL [γ-³³P]-ATP 的40 μM ATP 溶液開始反應(yīng)，反應(yīng)在室溫下溫和混合進(jìn)行2小時(shí)。加入 5μL 25 mM EDTA儲(chǔ)存液終止反應(yīng)。不使用洗滌劑清洗實(shí)驗(yàn)板，而使用384孔實(shí)驗(yàn)板洗滌器，然后每孔加入25μL UltimaGold 閃爍使用BetaPlate液體閃爍計(jì)數(shù)器測(cè)定滲透進(jìn)固定化PI底物的放射性。
細(xì)胞實(shí)驗(yàn)	細(xì)胞系	KPL4, BT474, T47D, BT20, MCF7, MDA-MB-468, SK-Br-3, LNCaP, PC3, Colo205, HT29, HCT116, A549, H460, U87MG, 786O.
	濃度	0.0, 0.003, 0.01, 0.03, 0.1, 0.3, 1.0, 3.0 和 10 μM
	孵育時(shí)間	72 小時(shí)
	方法	藥物處理72小時(shí)后，使用Cell Titer-Glo 發(fā)光法細(xì)胞活力檢測(cè)試劑盒測(cè)定細(xì)胞增殖。細(xì)胞按每孔500-1000個(gè)細(xì)胞接種到 384孔板中，孔中含 25 μL 生長(zhǎng)培養(yǎng)基。對(duì)于每種細(xì)胞系的測(cè)定，細(xì)胞接種到單獨(dú)的實(shí)驗(yàn)板上，在t=0小時(shí)和t=72小時(shí)測(cè)定發(fā)光值。在37°C下溫育過夜，每孔加入25μL Cell Titer-Glo 溶液測(cè)定t=0時(shí)樣品的發(fā)光值，轉(zhuǎn)移實(shí)驗(yàn)板到搖床上，在室溫下進(jìn)行10分鐘，然后使用發(fā)光檢測(cè)儀（最大光檢測(cè)在428 nm處測(cè)定）在Wallac Victor2 1420 Multilable HTS計(jì)數(shù)板上對(duì)實(shí)驗(yàn)板進(jìn)行讀數(shù)。使用在生長(zhǎng)培養(yǎng)基中稀釋的化合物（終體積為30 μL）處理t=72小時(shí)的劑量板。細(xì)胞在37°C下溫育72小時(shí)。每孔加入30μL Cell Titer-Glo溶液測(cè)定t=72小時(shí)樣品的發(fā)光值，然后將細(xì)胞置于搖床上在室溫下進(jìn)行10分鐘，然后使用Victor發(fā)光檢測(cè)儀讀讀取發(fā)光值。進(jìn)行數(shù)據(jù)處理，實(shí)驗(yàn)組和對(duì)照組中t=72小時(shí)發(fā)光值減去t=0時(shí)發(fā)光值。實(shí)驗(yàn)組和對(duì)照組的發(fā)光值百分比差異用來(lái)測(cè)定生長(zhǎng)抑制百分?jǐn)?shù)。
實(shí)驗(yàn)圖片	檢測(cè)方法	檢測(cè)指標(biāo)	實(shí)驗(yàn)圖片	PMID
	Western blot	p-AKT / AKT / p-PRAS40(T246) / p-GSK3β(S9) / cleaved caspase-3 / cleaved caspase-7 / PI3K-p85 p-FoxO4(T28) / p-S6(S235/236) / p-4E-BP1(S65) / p-4E-BP1(T37/46) / p-HER3(Y1197) / HER3 / p-IGF1Rβ/ IGF1R / p-HER2 / p-EGFR / p-STAT3 / p-ERK		24436048
	Growth inhibition assay	Cell viability		24436048

體內(nèi)研究(In Vivo)
體內(nèi)研究活性	BAY 80-6946 耐受性良好，MTD(最大耐受劑量)為0.8 mg/kg。PK（藥代動(dòng)力學(xué)）研究結(jié)果支持每周給藥。按MTD處理，在第一個(gè)24小時(shí)期間出現(xiàn)2/3級(jí)高血糖。PK, 臨床SD和FDG-PET 數(shù)據(jù)與有效處理和PI3K 通路抑制情況一致。^[1]

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試驗(yàn)信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05082025	Active not recruiting	Endometrial Cancer\|Ovarian Cancer	M.D. Anderson Cancer Center\|Bayer	September 27 2022	Phase 2
NCT05217914	Active not recruiting	Relapsed or Refractory Indolent Non-Hodgkin Lymphoma	Bayer	July 1 2022	--
NCT04939272	Suspended	Recurrent Mantle Cell Lymphoma\|Refractory Mantle Cell Lymphoma	City of Hope Medical Center\|National Cancer Institute (NCI)	June 29 2022	Phase 1\|Phase 2
NCT04572763	Active not recruiting	Diffuse Large B Cell Lymphoma\|Relapsed Diffuse Large B-Cell Lymphoma\|Refractory Diffuse Large B-Cell Lymphoma	Dana-Farber Cancer Institute\|AbbVie\|Bayer	September 8 2021	Phase 1\|Phase 2
NCT04803123	Terminated	Leukemia Acute Lymphocytic	Dorothy Sipkins MD PhD\|Bayer\|Duke University	June 21 2021	Early Phase 1

參考文獻(xiàn)
https://pubmed.ncbi.nlm.nih.gov/24170767/ https://pubmed.ncbi.nlm.nih.gov/25528022/

參考文獻(xiàn)

https://pubmed.ncbi.nlm.nih.gov/24170767/
https://pubmed.ncbi.nlm.nih.gov/25528022/

化學(xué)信息&溶解度

分子量	480.52	分子式	C₂₃H₂₈N₈O₄
CAS號(hào)	1032568-63-0	SDF	Download Copanlisib (BAY 80-6946) SDF
Smiles	COC1=C(C=CC2=C3NCCN3C(=NC(=O)C4=CN=C(N=C4)N)N=C21)OCCCN5CCOCC5
儲(chǔ)存條件(自收到貨起)	3年-20°C粉狀	儲(chǔ)備液保存和期限建議分裝儲(chǔ)備液，避免反復(fù)凍融！	1年-80°C溶于溶劑
儲(chǔ)存條件(自收到貨起)	3年-20°C粉狀	儲(chǔ)備液保存和期限建議分裝儲(chǔ)備液，避免反復(fù)凍融！	1個(gè)月-20°C溶于溶劑

體外溶解度
批次：

5%TFA : 6.01 mg/mL (12.5 mM)

Ethanol : 0.01 mg/mL (0.02 mM)

Water : 0.002 mg/mL (0.0 mM)

5%TFA : 8 mg/mL (16.64 mM)

DMSO : Insoluble ( ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開封DMSO)

Water : Insoluble

DMSO : Insoluble ( ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開封DMSO)

Water : Insoluble

Ethanol : Insoluble

DMSO : Insoluble ( ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開封DMSO)

Water : Insoluble

Ethanol : Insoluble

5%TFA : 3.78 mg/mL (7.86 mM)

Ethanol : 0.01 mg/mL (0.02 mM)

DMSO : 0.002 mg/mL ( (0.0 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開封DMSO)

摩爾濃度計(jì)算器

體內(nèi)溶解配方
批次：

現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑

動(dòng)物體內(nèi)配方計(jì)算器

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量	濃度	體積	分子量
=	×	×

稀釋計(jì)算器分子量計(jì)算器

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過程中的損耗，建議多配一只動(dòng)物的藥量）

給藥劑量 mg/kg 動(dòng)物平均體重 g 每只動(dòng)物給藥體積 μL 動(dòng)物數(shù)量只

第二步：請(qǐng)輸入動(dòng)物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO + % + % Tween 80 + % ddH2O

%DMSO+ %

計(jì)算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過該批次藥物DMSO溶解度，請(qǐng)先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH₂O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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* 必填項(xiàng)

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Copanlisib (BAY 80-6946)

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