125I-SDF-CXCR4 ( IC50 = 13 nM ); HIV-1 (NL4.3 strain) ( IC50 = 1 nM ); HIV-1 (NL4.3 strain) ( IC50 = 9 nM ); HIV-1 (NL4.3 strain) ( IC50 = 3 nM ); HIV-1 (NL4.3 strain) ( IC50 = 26 nM )

体外活性：AMD-070 对 MT-4 细胞中的 HIV-1、HIV-1 IIIb X4 株有活性，AMD-070 的 IC50 值高出 9 倍（0.009 μM vs 0.001 μM）和 8.7-与 MT-4 细胞相比，PBMC 中的浓度高出一倍（0.003 μM vs 0.026 μM）。 AMD-070具有抗病毒能力，IC50值为15.5 nM。激酶测定：首先将 SUP-T1 T 细胞与化合物（以 1 作为对照）在冰上预孵育 30 分钟，用含 2% FCS 的 PBS 洗涤，并与 PE 缀合的抗 CXCR4 mAb 在冰上孵育 30 分钟。用 PBS 洗涤后，用 1% 多聚甲醛的 PBS 溶液固定细胞样品，并在 FACS Calibur 流式细胞仪上进行分析。使用平均荧光强度值确定化合物对 mAb 结合的剂量依赖性抑制作用。细胞测定：激活的细胞（PHA刺激的母细胞）用PBS洗涤3次，完成病毒感染。 HIV 感染或模拟感染的 PHA 刺激的母细胞在 25 U/mL IL-2 和不同浓度的化合物存在下培养。第10天收集上清液，并通过p24病毒Ag ELISA试剂盒分析培养物上清液中的HIV-1核心抗原。如前所述进行MT-4细胞中HIV-1复制的抑制。抗 HIV-1 活性和细胞毒性测量同时进行。它们基于感染 HIV-1 的 MT-4 细胞在不同浓度的测试化合物存在下的活力。 ICsub>50定义为抑制50%的病毒感染细胞抵抗病毒细胞病变所需的浓度。

AMD-070 在大鼠和狗中显示出良好的口服生物利用度。清除率取决于物种，与大鼠相比，AMD-070 在狗体内的清除率较低。

Absorption
In adults with WHIM syndrome, the mean (CV%) Cmax at steady-state is 3304 (58.6%) ng/mL and the AUC from 0 to 24 hours (AUC0-24h) is 13970 (58.4%) ngxh/mL following 400 mg once daily. Mavorixafor demonstrates nonlinear pharmacokinetics with greater than dose-proportional increases in Cmax and AUC0-24h over a dose range of 50 mg (0.125 times the recommended dosage) to 400 mg. Mavorixafor steady-state is reached after approximately 9 to 12 days at the highest approved recommended dosage in healthy subjects. Mavorixafor median (range) Tmax is 2.8 hours (1.9 to 4 hours) at the highest approved recommended dosage. Food decreases Cmax and AUC.

Route of Elimination
After a single oral dose of radiolabeled mavorixafor, 74.2% of the administered dose was recovered out of which 61.0% of administered radioactivity was recovered in feces and 13.2% (3% unchanged) was recovered in the urine over the 240-hour collection period in healthy subjects.

Volume of Distribution
Mavorixafor volume of distribution was 768 L in adults with WHIM syndrome.

Clearance
The mean (CV%) apparent clearance was 62 L/h (40%) following a single-dose administration of mavorixafor 400 mg in healthy subjects. Mavorixafor exhibits at least partial nonlinear apparent clearance; however, this is not clinically significant at the approved recommended dosage.

Protein Binding
In vitro, mavorixafor is >93% bound to human plasma proteins.

Metabolism / Metabolites
Mavorixafor is metabolized by CYP3A4 and, to a lesser extent, CYP2D6.

Biological Half-Life
The mean (CV%) terminal half-life was 82 h (34%) following a single-dose administration of mavorixafor 400 mg in healthy subjects.

Mavorixafor (AMD070) is an orally bioavailable small molecule; good oral bioavailability was observed in both rats and dogs [1]
- In CD-1 mice, after oral administration of Mavorixafor (AMD070) at 400 μg/animal, the drug was detected in the lung tissue, and its concentration varied over time, with the EC₉₀ (44 ng/mL) used as a reference threshold for pharmacodynamic activity [2]
- In C57BL/6 mice, following intraperitoneal administration of Mavorixafor (AMD070), the drug was distributed in plasma, liver, and lung tissues, with measurable concentrations at different time points [2]

Mavorixafor (AMD070) was noncytotoxic to MT-4 cells and PBMCs at concentrations exceeding 23 μM in vitro [1]

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of mavorixafor during breastfeeding. The manufacturer recommends not breastfeeding treatment and for three weeks after the final dose.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

PLoS One.2016 Mar 21;11(3):e0151765;J Med Chem.2010 Apr 22;53(8):3376-88.

Mavorixafor is a CXC chemokine receptor 4 (CXCR4) antagonist. It was first approved by the FDA on April 30, 2024, for the treatment of warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a genetic immunodeficiency disorder characterized by a reduced number of mature neutrophils and lymphocytes. WHIM syndrome is caused by mutations in the CXCR4 gene, which leads to overactivation of CXCR4 signalling pathways. Mavorixafor prevents the activation of CXCR4. As CXCR4 mutations have also been implicated in human immunodeficiency virus (HIV), Waldenstrom’s macroglobulinemia (WM), B-cell non-Hodgkin lymphoma, and solid tumours, including melanoma, mavorixafor is being investigated in these conditions.
Mavorixafor is a CXC Chemokine Receptor 4 Antagonist. The mechanism of action of mavorixafor is as a CXC Chemokine Receptor 4 Antagonist, and Cytochrome P450 2D6 Inhibitor, and Cytochrome P450 3A4 Inhibitor, and P-Glycoprotein Inhibitor.
Mavorixafor is an orally bioavailable inhibitor of C-X-C chemokine receptor type 4 (CXCR4), with potential antineoplastic and immune checkpoint inhibitory activities. Upon administration, mavorixafor selectively binds to CXCR4 and prevents the binding of CXCR4 to its ligand, stromal cell-derived factor 1 (SDF-1 or CXCL12). This inhibits receptor activation and results in decreased proliferation and migration of CXCR4-overexpressing tumor cells. In addition, inhibition of CXCR4 prevents the recruitment of regulatory T-cells and myeloid-derived suppressor cells (MDSCs) to the tumor microenvironment, thereby abrogating CXCR4-mediated immunosuppression and enabling the activation of a cytotoxic T-lymphocyte-mediated immune response against cancer cells. The G protein-coupled receptor CXCR4, which is upregulated in several tumor cell types, induces the recruitment of immunosuppressive cells in the tumor microenvironment, suppresses immune surveillance, and promotes tumor angiogenesis and tumor cell proliferation. It is also a co-receptor for HIV entry into T-cells.
MAVORIXAFOR is a small molecule drug with a maximum clinical trial phase of IV (across all indications) that was first approved in 2024 and is indicated for neoplasm and has 6 investigational indications.
a derivative of AMD3100; a CXCR4 blocker

C21H28CLN5

385.933523178101

385.203

880549-30-4

558447-26-0;880549-30-4 (HCl); 2309699-17-8

71576687

Light yellow to brown solid at room temperature

5.078

70.83

3

4

7

27

431

1

N([C@H]1CCCC2C=CC=NC1=2)(CCCCN)CC1=NC2C=CC=CC=2N1.Cl

DBNMEMJSDAAGNZ-FYZYNONXSA-N

InChI=1S/C21H27N5.ClH/c22-12-3-4-14-26(15-20-24-17-9-1-2-10-18(17)25-20)19-11-5-7-16-8-6-13-23-21(16)19;/h1-2,6,8-10,13,19H,3-5,7,11-12,14-15,22H2,(H,24,25);1H/t19-;/m0./s1

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

---

注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

View More

注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

---

口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

View More

口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

---

注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。