VAL-083
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MedKoo CAT#: 205920

CAS#: 23261-20-3

Description: VAL-083 is a bi-functional alkylating agent, with potential antineoplastic activity. Upon administration, VAL-083 crosses the blood brain barrier (BBB) and appears to be selective for tumor cells. This agent alkylates and crosslinks DNA which ultimately leads to a reduction in cancer cell proliferation. In addition, VAL-083 does not show cross-resistance to other conventional chemotherapeutic agents and has a long half-life in the brain.

Chemical Structure

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VAL-083
CAS# 23261-20-3
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 205920
Name: VAL-083
CAS#: 23261-20-3
Chemical Formula: C6H10O4
Exact Mass: 146.06
Molecular Weight: 146.140
Elemental Analysis: C, 49.31; H, 6.90; O, 43.79

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3750 Ready to ship
2g USD 6250 Ready to ship
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Synonym: VAL083; VAL083; VAL083; Dianhydrodulcitol; Dianhydrogalactitol; Dulcitol Diepoxide;

IUPAC/Chemical Name: (1R,2S)-1-((R)-oxiran-2-yl)-2-((S)-oxiran-2-yl)ethane-1,2-diol

InChi Key: AAFJXZWCNVJTMK-GUCUJZIJSA-N

InChi Code: InChI=1S/C6H10O4/c7-5(3-1-9-3)6(8)4-2-10-4/h3-8H,1-2H2/t3-,4+,5+,6-

SMILES Code: O[C@@H]([C@@H]1OC1)[C@@H]([C@H]2OC2)O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: VAL-083 has demonstrated activity in cyclophosphamide, BCNU and phenylanine mustard resistant cell lines and no evidence of cross-resistance has been encountered in published clinical studies. Based on the presumed alkylating functionality of VAL-083, published literature suggests that DNA repair mechanisms associated with Temodar and nitrosourea resistance, such as 06-methylguanine methyltransferace (MGMT), may not confer resistance to VAL-083.  VAL-083 readily crosses the blood brain barrier where it maintains a long half-life in comparison to the plasma. Published preclinical and clinical research demonstrates that VAL-083 is selective for brain tumor tissue.  VAL-083 has been assessed in multiple studies as chemotherapy in the treatment of newly diagnosed and recurrent brain tumors. In published clinical studies, VAL-083 has previously been shown to have a statistically significant impact on median survival in high grade gliomas when combined with radiation vs. radiation alone. The main dose-limiting toxicity related to the administration of VAL-083 in previous clinical studies was myelosuppression.  (source: http://www.delmarpharma.com/product_development_programs/val083/).       

Biological target: VAL-083 is an alkylating agent that creates N7 methylation on DNA.
In vitro activity: In this study’s cohort, VAL-083 was significantly more effective than TMZ (Fig. 6a, b) and the response was not dependent on MGMT promoter methylation status (Fig. 6c). The response was similar in treatment-naïve and relapsed organoids (Supplementary Fig. 6c, online resource), suggesting that VAL-083 is able to overcome TMZ resistance. Reference: Acta Neuropathol. 2020; 140(6): 919–949. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666297/
In vivo activity: VAL-083 monotherapy led to a dramatic reduction in tumor growth (Fig. 6e), an effect which was only mildly accentuated by combined treatment. Histological assessment of tumor-containing mouse brains confirmed the strong reduction in tumor volume upon VAL-083 treatment (Supplementary Fig. 6e, online resource). This was paralleled by an increase in DNA damage in tumor cells, determined by H2AX phosphorylation (H2AX-P) (Supplementary Fig. 6f, online resource). Limited H2AX-P was also seen in normal brain cells close to the meninges and the subventricular zone, but to a much lower extent than in tumor cells. In summary, this study shows that VAL-083 has a consistently favorable drug profile against GBM; thus, representing a promising candidate for GBM treatment either alone or in combination with antiangiogenic compounds. Reference: Acta Neuropathol. 2020; 140(6): 919–949. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666297/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 100.0 684.28
Water 50.0 342.14

Preparing Stock Solutions

The following data is based on the product molecular weight 146.14 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Golebiewska A, Hau AC, Oudin A, Stieber D, Yabo YA, Baus V, Barthelemy V, Klein E, Bougnaud S, Keunen O, Wantz M, Michelucci A, Neirinckx V, Muller A, Kaoma T, Nazarov PV, Azuaje F, De Falco A, Flies B, Richart L, Poovathingal S, Arns T, Grzyb K, Mock A, Herold-Mende C, Steino A, Brown D, May P, Miletic H, Malta TM, Noushmehr H, Kwon YJ, Jahn W, Klink B, Tanner G, Stead LF, Mittelbronn M, Skupin A, Hertel F, Bjerkvig R, Niclou SP. Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology. Acta Neuropathol. 2020 Dec;140(6):919-949. doi: 10.1007/s00401-020-02226-7. Epub 2020 Oct 3. PMID: 33009951; PMCID: PMC7666297.
In vitro protocol: 1. Golebiewska A, Hau AC, Oudin A, Stieber D, Yabo YA, Baus V, Barthelemy V, Klein E, Bougnaud S, Keunen O, Wantz M, Michelucci A, Neirinckx V, Muller A, Kaoma T, Nazarov PV, Azuaje F, De Falco A, Flies B, Richart L, Poovathingal S, Arns T, Grzyb K, Mock A, Herold-Mende C, Steino A, Brown D, May P, Miletic H, Malta TM, Noushmehr H, Kwon YJ, Jahn W, Klink B, Tanner G, Stead LF, Mittelbronn M, Skupin A, Hertel F, Bjerkvig R, Niclou SP. Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology. Acta Neuropathol. 2020 Dec;140(6):919-949. doi: 10.1007/s00401-020-02226-7. Epub 2020 Oct 3. PMID: 33009951; PMCID: PMC7666297.
In vivo protocol: 1. Golebiewska A, Hau AC, Oudin A, Stieber D, Yabo YA, Baus V, Barthelemy V, Klein E, Bougnaud S, Keunen O, Wantz M, Michelucci A, Neirinckx V, Muller A, Kaoma T, Nazarov PV, Azuaje F, De Falco A, Flies B, Richart L, Poovathingal S, Arns T, Grzyb K, Mock A, Herold-Mende C, Steino A, Brown D, May P, Miletic H, Malta TM, Noushmehr H, Kwon YJ, Jahn W, Klink B, Tanner G, Stead LF, Mittelbronn M, Skupin A, Hertel F, Bjerkvig R, Niclou SP. Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology. Acta Neuropathol. 2020 Dec;140(6):919-949. doi: 10.1007/s00401-020-02226-7. Epub 2020 Oct 3. PMID: 33009951; PMCID: PMC7666297.

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1: Szende B, Jeney A, Institoris L. The diverse modification of N-butyl-N-(4-hydroxybutyl) nitrosamine induced carcinogenesis in urinary bladder by dibromodulcitol and dianhydrodulcitol. Acta Morphol Hung. 1992;40(1-4):187-93. PubMed PMID: 1365762.

2: Anderlik P, Szeri I, Bános Z. Bacterial translocation in dianhydrodulcitol-treated mice. Acta Microbiol Hung. 1988;35(1):49-54. PubMed PMID: 3293340.

3: Huang ZG. [Clinical observation of 15 cases of chronic myelogenous leukemia treated with 1,2,5,6-dianhydrodulcitol]. Zhonghua Nei Ke Za Zhi. 1982 Jun;21(6):356-8. Chinese. PubMed PMID: 6957285.

4: Anderlik P, Szeri I, Bános Z, Wessely M, Radnai B. Higher resistance of germfree mice to dianhydrodulcitol, a lymphotropic cytostatic agent. Acta Microbiol Acad Sci Hung. 1982;29(1):33-40. PubMed PMID: 6211912.

5: Bános Z, Szeri I, Anderlik P. Effect of Bordetella pertussis vaccine on the course of lymphocytic choriomeningitis (LCM) virus infection in suckling mice pretreated with dianhydrodulcitol (DAD). Acta Microbiol Acad Sci Hung. 1979;26(2):121-5. PubMed PMID: 539467.

6: Bános Z, Szeri I, Anderlik P. Dianhydrodulcitol treatment of lymphocytic choriomeningitis virus infection in suckling mice. Acta Microbiol Acad Sci Hung. 1979;26(1):29-34. PubMed PMID: 484266.

7: Gerö-Ferencz E, Tóth K, Somfai-Relle S, Gál F. Effect of dianhydrodulcitol (DAD) on the primary immune response of normal and tumor bearing rats. Oncology. 1977;34(4):150-2. PubMed PMID: 335301.

8: Kopper L, Lapis K, Institóris L. Incorporation of 3H-dibromodulcitol and 3H-dianhydrodulcitol into ascites tumor cells. Autoradiographic study. Neoplasma. 1976;23(1):47-52. PubMed PMID: 1272473.

9: Bános S, Szeri I, Anderlik P. Combined phytohaemagglutinin and dianhydrodulcitol treatment of lymphocytic choriomeningitis virus infection in mice. Acta Microbiol Acad Sci Hung. 1975;22(3):237-40. PubMed PMID: 1155228.