Physicochemical Properties
| Molecular Formula | C119H193N53O20S |
| Molecular Weight | 2718.21383547783 |
| Exact Mass | 2717.546 |
| CAS # | 917953-08-3 |
| Related CAS # | HXR9 hydrochloride |
| PubChem CID | 168013268 |
| Appearance | Typically exists as solid at room temperature |
| LogP | -10 |
| Hydrogen Bond Donor Count | 52 |
| Hydrogen Bond Acceptor Count | 35 |
| Rotatable Bond Count | 100 |
| Heavy Atom Count | 193 |
| Complexity | 5940 |
| Defined Atom Stereocenter Count | 18 |
| SMILES | CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)NC(=O)[C@H](CC3=CNC4=CC=CC=C43)NC(=O)[C@@H]5CCCN5C(=O)[C@H](CC6=CC=C(C=C6)O)NC(=O)[C@H](CC7=CNC8=CC=CC=C87)N |
| InChi Key | CHEKUKKHAYMCIJ-BVRAJVGYSA-N |
| InChi Code | InChI=1S/C119H193N53O20S/c1-193-53-40-86(166-105(186)88(56-67-60-153-75-23-5-3-21-72(67)75)170-108(189)92-35-19-52-172(92)109(190)91(54-65-36-38-70(173)39-37-65)171-93(174)73(122)55-66-59-152-74-22-4-2-20-71(66)74)104(185)157-76(24-6-8-41-120)94(175)156-77(25-7-9-42-121)103(184)168-90(58-69-62-142-64-155-69)107(188)169-89(57-68-61-141-63-154-68)106(187)165-84(32-16-49-149-117(135)136)101(182)163-82(30-14-47-147-115(131)132)99(180)161-80(28-12-45-145-113(127)128)97(178)159-78(26-10-43-143-111(123)124)95(176)158-79(27-11-44-144-112(125)126)96(177)160-81(29-13-46-146-114(129)130)98(179)162-83(31-15-48-148-116(133)134)100(181)164-85(33-17-50-150-118(137)138)102(183)167-87(110(191)192)34-18-51-151-119(139)140/h2-5,20-23,36-39,59-64,73,76-92,152-153,173H,6-19,24-35,40-58,120-122H2,1H3,(H,141,154)(H,142,155)(H,156,175)(H,157,185)(H,158,176)(H,159,178)(H,160,177)(H,161,180)(H,162,179)(H,163,182)(H,164,181)(H,165,187)(H,166,186)(H,167,183)(H,168,184)(H,169,188)(H,170,189)(H,171,174)(H,191,192)(H4,123,124,143)(H4,125,126,144)(H4,127,128,145)(H4,129,130,146)(H4,131,132,147)(H4,133,134,148)(H4,135,136,149)(H4,137,138,150)(H4,139,140,151)/t73-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-/m0/s1 |
| Chemical Name | (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-methylsulfanylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoic acid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | HXR9 (60μM; 4 hours) inhibits PBX and HOX interaction[1]. B16 and primary melanoma cells undergo apoptosis when exposed to HXR9 (60μM; 2 hours)[1]. Certain transcriptional alterations are induced by HXR9 (60μM; 2 hours)[1]. HXR9 (B16 cells) has 20μM IC50 antiproliferative activity[1]. |
| ln Vivo | HXR9 inhibits the growth of A549 tumors in vivo when administered intraperitoneally twice weekly for eighteen days at an initial dose of 100 mg/kg followed by a dosing of 10 mg/kg twice weekly[3]. |
| Cell Assay |
Western Blot Analysis Cell Types: murine B16melanoma cells Concentration Experimental Results: Blocked the binding of HOXD9 to PBX. Apoptosis Analysis Cell Types: B16 cells Tested Concentrations: 60 μM Incubation Duration: 2 hrs (hours) Experimental Results: A significant proportion of cells were in late phases of apoptosis. RT- PCR Cell Types: B16F10cells Tested Concentrations: 60 μM Incubation Duration: 2 hrs (hours) Experimental Results: Fos, Jun, Dusp1, and Atf1, were all Dramatically up-regulate. |
| Animal Protocol |
Animal/Disease Models: C57black/6 mice (bearing B16 cells) Doses: 10 mg/kg Route of Administration: Iv via the tail vein; twice weekly (~30 days) Experimental Results: Tumors demonstrated a significant degree of growth retardation. Animal/Disease Models: Athymic nude mice (bearing A549 cells) Doses: Initial dose of 100 mg/kg (subsequent dosing of 10 mg/ kg twice weekly) Route of Administration: Intraperitoneal; twice weekly for 18 days Experimental Results: The tumors of HXR9-treated mice were considerably smaller than those of the control groups. |
| References |
[1]. Morgan R, et al. Antagonism of HOX/PBX dimer formation blocks the in vivo proliferation of melanoma. Cancer Res. 2007;67(12):5806-5813. [2]. Li Z, et al. PBX3 is an important cofactor of HOXA9 in leukemogenesis. Blood. 2013;121(8):1422-1431. [3]. Plowright L, et al. HOX transcription factors are potential therapeutic targets in non-small-cell lung cancer (targeting HOX genes in lung cancer). Br J Cancer. 2009;100(3):470-475. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.3679 mL | 1.8394 mL | 3.6789 mL | |
| 5 mM | 0.0736 mL | 0.3679 mL | 0.7358 mL | |
| 10 mM | 0.0368 mL | 0.1839 mL | 0.3679 mL |