2. Apoptosis PI3K/Akt/mTOR JAK/STAT Signaling Stem Cell/Wnt NF-κB
  3. Apoptosis Akt mTOR STAT NF-κB
  4. HBS-101

HBS-101 是一种具有选择性、口服活性、可穿透血脑屏障的 Midkine (MDK) 抑制剂 (KD = 38.4 nmol/L)。HBS-101 显著降低细胞活力、克隆形成存活率、侵袭性，并增加细胞凋亡 (apoptosis)。HBS-101 涉及抑制 Akt/mTOR、STAT3 和 NF-κB 通路。HBS-101 可用于三阴性乳腺癌 (TNBC) 的研究。

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HBS-101

HBS-101 Chemical Structure

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HBS-101 相关抗体

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  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

HBS-101 is a selectively, orally active, brain-penetrant, Midkine (MDK) inhibitor (KD = 38.4 nM). HBS-101 significantly reduces cell viability, clonogenic survival, and invasiveness and increases apoptosis. HBS-101 involves suppression of the Akt/mTOR, STAT3, and NF-κB pathways. HBS-101 can be used for the study of Triple-negative breast cancer (TNBC)[1].

体外研究
(In Vitro)

HBS-101 (0.1-10 μM，5 天) 显著降低 TNBC 细胞系的细胞活力[1]。
HBS-101 (0-5 μM) 以剂量依赖性方式降低 TNBC 细胞的集落形成能力[1]。
HBS-101 (20 μM，24 小时) 诱导 TNBC 细胞凋亡，但不诱导正常乳腺上皮细胞凋亡[1]。
HBS-101 (20 μM，20 小时) 显著降低 HCC-70 细胞中 MDK 受体 (特别是 Notch2) 的表达；抑制下游信号通路，包括 mTOR、STAT3和NF-κB；并提高裂解Caspase-3的水平[1]。
HBS-101 (20 μM，24 小时) 下调 MDK 靶基因，并显著降低稳定表达这些报告基因的 TNBC 细胞中的 STAT3 和 NF-κB 报告基因活性[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

HBS-101 相关抗体:

Cell Viability Assay[1]

Cell Line: SUM-159, BT-549, MDA-MB-468, MDA-MB-231, MDA-MB-231-BrM2-831, HCC-70, HCC-1937, HER2+ SKBR3, ER+ MCF7, MCF10A
Concentration: 0.1 μM, 1 μM, 10 μM
Incubation Time: 5 days
Result: Significantly inhibited the viability of TNBC cell lines, with IC50 values ranging from 0.3 to 2.8 μmol/L.
Exhibited weaker inhibitory effects on HER2+ SKBR3, (IC50 ~ 16 μM) and ER+MCF7, (IC50 > 20 μM) breast cancer cell lines.
Showed no toxicity against normal breast epithelial MCF10A cells.

Western Blot Analysis[1]

Cell Line: HCC-70 cells
Concentration: 20 μM
Incubation Time: 20 h
Result: Reduced Notch2 receptor protein levels.
Inhibited the phosphorylation of mTOR, STAT3, and NF-κB, and increased the level of cleaved caspase-3, a marker of apoptosis.

RT-PCR[1]

Cell Line: MDA-MB-231 cells, BT-549 cells
Concentration: 20 μM
Incubation Time: 20 h
Result: Significantly reduced STAT3 and NF-κB reporter activity in TNBC cells that stably express these reporters.

Cell Invasion Assay[1]

Cell Line: MDA-MB-231 cells, BT-549 cells, MCF10A cells
Concentration: 20 μM
Incubation Time: 24 h
Result: Induced apoptosis in TNBC cells, but not in normal mammary epithelial cells.
体内研究
(In Vivo)

HBS-101 (1 mg/kg (静脉注射)，10 mg/kg (口服) 在大鼠体内具有快速的体内代谢动力学和极高的口服生物利用度[1]。
HBS-101 (10 mg/kg，腹腔注射) 在小鼠中可快速吸收并有效穿透血脑屏障[1]。
HBS-101 (2-10 mg/kg，口服，5 天) 在小鼠中连续 5 天以高达 10 mg/kg (口服) 的剂量给药是安全的，并且不会产生可观察到的器官毒性[1]。
HBS-101 (2 mg/kg，5 mg/kg，口服，5 天) 在小鼠中口服给药可有效抑制 TNBC 原位肿瘤的生长，5 mg/kg 被确定为最低有效剂量[1]。
HBS-101 (5 mg/kg，口服，每周 5 天) 可降低 MDA-MB-231 细胞荷瘤小鼠肿瘤的增殖活性[1]。
HBS-101 (10 mg/kg，腹腔注射，每周 5 天) 在小鼠脑转移模型中表现出强大的抗肿瘤活性[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Rats[1].
Dosage: 1 mg/kg, 10 mg/kg
Administration: I.v., p.o.
Result: Had monoexponential disposition in vivo and had an estimated plasma half-life between 0.7 and 1.6 hours.
Had excellent oral bioavailability in rats.
Animal Model: Female C57BL/6 mice[1].
Dosage: 10 mg/kg
Administration: I.p., once
Result: Absorbed rapidly following i.p. administration, resembling an i.v. bolus drug administration.
Detected in the brain, with peak detectable levels reaching 1,654 ng/g 10 minutes after administration, suggesting that HBS-101 effectively crosses the blood-brain barrier.
Animal Model: Female C57BL/6 mice[1].
Dosage: 2 mg/kg, 5 mg/kg, 10 mg/kg
Administration: P.o., 5 days
Result: No abnormalities were detected during the gross pathological examination of the animals.
Animal Model: MDA-MB-231 cells (2 × 106) mixed with a 1:1 volume of Matrigel were injected into the mammary fat pad of the nude mice[1].
Dosage: 2 mg/kg, 5 mg/kg
Administration: P.o., 5 times a week
Result: Led to a significant dose-dependent reduction in tumor volume.
Not affected mouse body weight.
Significant decreased in Ki-67–positive cells.
Animal Model: Female SCID mice were used as recipients for 2 mm3 TNBC–PDX-96 tumor tissue implants to establish subcutaneous PDX tumor models[1].
Dosage: 5 mg/kg
Administration: P.o., 5 times a week
Result: Significantly inhibited PDX tumor growth, with tumor volume and weight significantly reduced. Significant decrease in Ki-67-positive cells.
Animal Model: 1.75 × 105 brain-metastatic MDA-MB-231-BrM2-831 cells were orthotopically injected into the right cerebral hemisphere of female NOD.CB17-Prkdcscid/NCrCrl mice[1].
Dosage: 10 mg/kg
Administration: I.p., 5 times a week
Result: Significantly reduced tumor progression and extended the survival of mice with orthotopic tumors.
分子量

346.41

Formula

C21H24F2O2
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
纯度 & 产品资料
参考文献

HBS-101 相关分类

  • 摩尔计算器

  • 稀释计算器

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

HBS-101HBS101HBS 101ApoptosisAktmTORSTATNF-κBPKBProtein kinase BMammalian target of RapamycinNuclear factor-κBNuclear factor-kappaBMidkineMDKTriple-Negative Breast CancerTNBCSTAT3Blood-Brain BarrierInhibitorinhibitorinhibit

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