Cridanimod (XBIO-101; XBIO101; Virexxa) is a novel and potent immunomodulator and interferon inducer with antineoplastic activity. It acts as a progesterone receptor (PR) activator mediated through induction of IFNα and IFNβ expression. Cridanimod can increase progesterone receptor (PR) expression and is able to induce the expression of PR in endometrial cancer. This could increase the sensitivity of endometrial cancer cells to progestin monotherapy.
Physicochemical Properties
| Molecular Formula | C15H11NO3 |
| Molecular Weight | 253.257 |
| Exact Mass | 253.073 |
| CAS # | 38609-97-1 |
| Related CAS # | 58880-43-6 (sodium);38609-97-1 (free acid); |
| PubChem CID | 38072 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 486.6±34.0 °C at 760 mmHg |
| Melting Point | -289ºC (dec.) |
| Flash Point | 248.1±25.7 °C |
| Vapour Pressure | 0.0±1.3 mmHg at 25°C |
| Index of Refraction | 1.657 |
| LogP | 2.03 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 19 |
| Complexity | 356 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | UOMKBIIXHQIERR-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C15H11NO3/c17-14(18)9-16-12-7-3-1-5-10(12)15(19)11-6-2-4-8-13(11)16/h1-8H,9H2,(H,17,18) |
| Chemical Name | 2-(9-oxoacridin-10(9H)-yl)acetic acid |
| Synonyms | Cridanimod XBIO101 CycloferonXBIO-101 Virexxa Cyclopheron XBIO 101 |
| 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 Vivo | The duration of cridanimod (intramuscular; 1-6 mg; twice weekly) was noticeably greater. IFNα and -β are markedly and dose-dependently increased in mice when treated with crinanimod [1]. |
| Animal Protocol |
Animal/Disease Models: Athymic mice with hec50co cells [1]. 1] Doses: 1, 3, 6 mg Route of Administration: IM; twice weekly Experimental Results: Dramatically prolonged survival. |
| References |
[1]. Xenetic Biosciences Announces FDA Acceptance of Investigational New Drug Application to Initiate Phase 2 Clinical Trial of Virexxa® in Endometrial Cancer. AUGUST 19, 2016. [2]. Cridanimod and progestin therapy in hormone-resistant endometrial cancer. Journal of Clinical Oncology, January 30, 2017. |
| Additional Infomation |
Cridanimod is a member of acridines. It is functionally related to an acridone. Cridanimod is a small molecule that can increase progesterone receptor (PR) expression, with potential antineoplastic adjuvant activity. Upon intramuscular administration, cridanimod is able to induce the expression of PR in endometrial cancer. This could increase the sensitivity of endometrial cancer cells to progestin monotherapy. In combination with a progestin, cancer cells could be eradicated through increased PR-mediated signaling, leading to an inhibition of luteinizing hormone (LH) release from the pituitary gland, via a negative feedback mechanism, and, eventually, an inhibition of estrogen release from the ovaries. This leads to an inhibition of cellular growth in estrogen-dependent tumor cells. In addition, this agent is able to increase the production and release of interferon (IFN) alpha and beta. PR is often downregulated in endometrial cancer and makes it resistant to progestin-mediated hormone therapy. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~493.56 mM) H2O : < 0.1 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (8.21 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (8.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9485 mL | 19.7426 mL | 39.4851 mL | |
| 5 mM | 0.7897 mL | 3.9485 mL | 7.8970 mL | |
| 10 mM | 0.3949 mL | 1.9743 mL | 3.9485 mL |