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Fig. 1 · Structure
Cat. No.
A15797
CAS No.
1297538-32-9
Formula
C19H19ClN6O2
Mol. Weight
398.85

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Darolutamide (ODM-201)

Cat. No. A15797 CAS 1297538-32-9

Androgen receptor antagonist

ODM-201 is a potent and full antagonists for human AR (hAR) with IC50 values of 26 nM by transactivation assays in AR-HEK293 cells.

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Publications for Darolutamide

1 publication citing this product

  1. Syeda Afshan, .et al. , Cancer Med, 2024, Sep;13(18):e70240 PMID: 39300962
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Biological Activity

Bioactivity / Mechanism

Darolutamide (ODM-201) binds androgen receptor and inhibits androgen-driven transcription. In the original discovery study, its reported Ki was 11 nM in a rat AR competition assay, while its IC50 was 26 nM in a human AR reporter assay. These are distinct assay endpoints. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target Activity Value
Androgen receptor Ki 11 nM

Cellular Effect

Cell Line Activity Value Description Reference
CWR22R IC50 > 30 μM Antiproliferative activity against human 22Rv1 expressing AR assessed as reduction in cell viability incubated for 6 days by CCK-8 assay [PMID: 31437779]
L02 IC50 > 30 μM Cytotoxicity against human L02 assessed as reduction in cell viability incubated for 6 days by CCK-8 assay [PMID: 31437779]
LNCaP IC50 1.65 μM Antiproliferative activity against human LNCAP expressing AR assessed as reduction in cell viability incubated for 6 days by CCK-8 assay [PMID: 31437779]
PC-3 IC50 > 30 μM Cytotoxicity against human PC3 assessed as reduction in cell viability incubated for 6 days by CCK-8 assay [PMID: 31437779]

In Vitro Studies

Darolutamide inhibited androgen-stimulated prostate cancer cell viability in a 6-day assay. Mean IC50 ± SD values were 410 ± 150 nM in VCaP, 500 ± 220 nM in LAPC-4 and 5,260 ± 2,510 nM in LNCaP cells (at least five biological replicates). The weaker LNCaP response underscores model-dependent activity. [2]

In a 72-hour LNCaP–fibroblast co-culture experiment, adding 1 μM darolutamide to an FRS2α inhibitor did not produce significant added inhibition over the FRS2α inhibitor alone. This negative combination finding is specific to the tested model and conditions. [3]

Competitive binding to rat androgen receptor

Biochemical assay · Wild-type AR in cytosolic lysates from rat ventral prostate [1]

ODM-201 displaced radiolabeled mibolerone with a reported Ki of 11 nM. This is an isolated-receptor binding endpoint, not a treatment dose or a human cellular IC50.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Competitive displacement of [3H]mibolerone from rat wtARKi 11 nM[1]

Literature-Reported Treatment Conditions

Treatment concentration
Increasing test-compound concentrations; 1 nM [3H]mibolerone
Exposure duration
Overnight incubation
Method
Cytosolic radioligand competition assay at 0–4 °C
Co-treatment
No drug combination; radioligand present
Reported limits
Solvent and exact concentration series not specified in the adopted text; quadruplicates are not asserted to be independent biological preparations.
Methods and source locations

Compound reported in the paper: Darolutamide (ODM-201); Compound label in the paper: ODM-201

Evidence for the named active compound in the reported model; no validation of an Adooq lot or of catalog stereochemical composition.

Results: High potency of ODM-201 to AR; Methods: Compounds and AR binding affinity; Fig. 1A/C and caption

Competitive displacement of [3H]mibolerone from rat wtAR: Competition binding with 1 nM [3H]mibolerone; bound radioactivity measured after separation of free ligand. Fig. 1C shows means of quadruplicates ± SEM. — Fig. 1C legend and caption; Results: High potency; Methods: AR binding affinity

Antagonism of human AR-dependent reporter activity

Cell-based study · AR-HEK293 cells stably expressing full-length human AR and an androgen-responsive luciferase reporter [1]

ODM-201 inhibited testosterone-stimulated reporter activity, with a reported IC50 of 26 nM. Reporter antagonism supports AR signaling inhibition under these assay conditions.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Inhibition of testosterone-stimulated androgen-responsive luciferaseIC50 26 nM[1]

Literature-Reported Treatment Conditions

Treatment concentration
Compound concentration-response with 0.45 nM testosterone
Exposure duration
24 hours
Method
Luciferase reporter assay in steroid-depleted medium
Co-treatment
No second therapeutic agent; testosterone is the agonist challenge
Reported limits
Exact solvent and complete concentration series not specified in adopted passages; triplicate points are not asserted to be biological replicates.
Methods and source locations

Compound reported in the paper: Darolutamide (ODM-201); Compound label in the paper: ODM-201

Evidence for the named active compound in the reported model; no validation of an Adooq lot or of catalog stereochemical composition.

Results: High potency of ODM-201 to AR; Methods: Cell lines, Compounds, Antagonism of ODM-201; Fig. 1D and caption

Inhibition of testosterone-stimulated androgen-responsive luciferase: Luciferase readout after 24 h with 0.45 nM testosterone; Fig. 1D points are means of triplicates ± SEM. — Fig. 1D legend/caption; Methods: Antagonism of ODM-201

Androgen-stimulated prostate cancer cell viability panel

Cell-based study · VCaP, LAPC-4 and LNCaP prostate cancer cells [2]

Darolutamide inhibited viability with model-dependent potency. LNCaP cells were less sensitive than VCaP and LAPC-4 cells; the authors relate this to the weaker response of AR T878A. These values must not be pooled with the shorter WST-1 assay reported in 2015.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Inhibition of VCaP cell viabilityIC50 (mean ± SD) 410 ± 150 nM[2]
Inhibition of LAPC-4 cell viabilityIC50 (mean ± SD) 500 ± 220 nM[2]
Inhibition of LNCaP cell viabilityIC50 (mean ± SD) 5,260 ± 2,510 nM[2]

Literature-Reported Treatment Conditions

Treatment concentration
Darolutamide concentration-response; R1881 0.1 nM (VCaP), 10 nM (LAPC-4), 1 nM (LNCaP)
Exposure duration
6 days
Method
ATP-based luminescent viability assay in charcoal-stripped FBS medium
Co-treatment
No drug combination; R1881 challenge
Reported limits
Exact darolutamide concentration series and solvent not specified in selected main passages.
Methods and source locations

Compound reported in the paper: Darolutamide (ODM-201); Compound label in the paper: Darolutamide

Evidence for the named active compound in the reported model; no validation of an Adooq lot or of catalog stereochemical composition.

Methods: Reagents, plasmids and cell lines; Cell viability and spheroid formation assays; Table 3 and footnote; Results: Strong in vitro efficacy

Inhibition of VCaP cell viability: 6-day CellTiter-Glo assay; 0.1 nM R1881. At least five biological replicates, with triplicate samples in the assay. — Table 3, Darolutamide row/VCaP column and footnote; Cell viability methods

Inhibition of LAPC-4 cell viability: 6-day CellTiter-Glo assay; 10 nM R1881. At least five biological replicates. — Table 3, Darolutamide row/LAPC-4 column and footnote; Cell viability methods

Inhibition of LNCaP cell viability: 6-day CellTiter-Glo assay; 1 nM R1881. At least five biological replicates. — Table 3, Darolutamide row/LNCaP column and footnote; Cell viability methods

Darolutamide plus FRS2α inhibitor in LNCaP–CAF co-culture

Cell-based study · 2D LNCaP prostate cancer cells co-cultured with PF179T cancer-associated fibroblasts (5:1 cancer-cell:CAF ratio) [3]

Adding 1 μM darolutamide to FRS2α inhibitor did not provide significant added proliferation or viability benefit over FRS2α inhibitor alone in this co-culture. This is a condition-specific negative combination result, not a universal absence of synergy or proof of darolutamide inactivity.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Added effect of darolutamide on FRS2α inhibitor suppression of proliferation/viabilityQualitative comparative outcome No significant added benefit over FRS2α inhibitor alone[3]

Literature-Reported Treatment Conditions

Treatment concentration
Darolutamide 1 μM; FRS2α inhibitor 3, 5 or 7 μM in viability panel; 5 and 7 μM in proliferation curves
Exposure duration
72 hours
Method
2D co-culture live-cell confluence imaging and luminescent viability assay
Vehicle
DMSO; corresponding controls 0.1%–0.2% for single/combination treatments
Co-treatment
Darolutamide plus FRS2α inhibitor (compound C7), with each single agent and vehicle controls
Reported limits
Main shared method gives 25 ng/mL FGF2 and 0.1–1 nM R1881; model-specific R1881 value not resolved. S6 caption font rendering malformed, so replicate number/error-bar definition and pairwise p values not asserted.
Methods and source locations

Compound reported in the paper: Darolutamide (ODM-201); Compound label in the paper: Darolutamide

Evidence for the named active compound in the reported model; no validation of an Adooq lot or of catalog stereochemical composition.

Methods 2.1–2.3; Results 3.7; Supplementary Fig. S6A and S6D (LNCaP group)

Added effect of darolutamide on FRS2α inhibitor suppression of proliferation/viability: Proliferation monitored by Incucyte over 72 h; viability by Cell Titre Glo 2.0 after 72 h. Fig. S6A/D and Results 3.7 support the qualitative conclusion; no numerical synergy score extracted. — Results 3.7; Supplementary Fig. S6A/D; Methods 2.3

In Vivo Studies

In male CB17-SCID mice bearing AR W742C-positive KuCaP-1 xenografts, oral darolutamide at 40 or 100 mg/kg twice daily reduced tumor growth versus vehicle. At day 68, tumor-growth increment relative to vehicle (% ΔT/ΔC) was 45% and 26%, respectively; only the higher dose met the paper’s ≤40% efficacy criterion. These values describe relative growth, not tumor regression. [2]

KuCaP-1 xenograft growth response

Animal study · CB17-SCID male mice bearing human KuCaP-1 prostate cancer xenografts with AR W742C [2]

Oral darolutamide reduced tumor growth relative to vehicle. The higher-dose arm met the paper’s efficacy criterion (% ΔT/ΔC ≤40%); the 40 mg/kg twice-daily arm yielded 45%, above that criterion. This model does not establish clinical resistance reversal.

Conditions shared by the study groups

Route
Oral (PO)
Frequency
Twice daily (BID)
Treatment course
Treatment started day 35 after inoculation; efficacy measured day 68
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
Darolutamide 40 mg/kg twice dailyVehicle-treated tumor-bearing mice; castration control shown separately in Fig. 4d–eDay 68 tumor-volume % ΔT/ΔC = 45%; p = 0.0169 versus vehicle (Fig. 4e). Reported maximal body-weight loss 8%; vehicle group loss 10%.[2]
Darolutamide 100 mg/kg twice dailyVehicle-treated tumor-bearing mice; castration control shown separately in Fig. 4d–eDay 68 tumor-volume % ΔT/ΔC = 26%; p = 0.0001 versus vehicle (Fig. 4e). Reported maximal body-weight loss 6%; vehicle group loss 10%.[2]
Darolutamide 40 mg/kg twice daily
Model: CB17-SCID male mice bearing human KuCaP-1 prostate cancer xenografts with AR W742C
Reported limits: Group n and vehicle composition not established in selected passages.
Darolutamide 100 mg/kg twice daily
Model: CB17-SCID male mice bearing human KuCaP-1 prostate cancer xenografts with AR W742C
Reported limits: Group n and vehicle composition not established in selected passages.
Methods and source locations

Compound reported in the paper: Darolutamide (ODM-201); Compound label in the paper: Darolutamide

Evidence for the named active compound in the reported model; no validation of an Adooq lot or of catalog stereochemical composition.

Methods: Animal studies; Results: Darolutamide shows strong in vivo efficacy in the KuCaP-1 prostate cancer xenograft; Fig. 4d–e and caption

Darolutamide 40 mg/kg twice daily · KuCaP-1 Results; Animal studies; Fig. 4d–e/caption

Darolutamide 100 mg/kg twice daily · KuCaP-1 Results; Animal studies; Fig. 4d–e/caption

Specifications

Manufacturer Adooq Bioscience
Actions Antagonist
CAS Number 1297538-32-9
Applications Androgen receptor antagonist
Formula C19H19ClN6O2
Molecular Weight 398.85
Synonyms BAY-1841788; ODM-201
SMILES
CC(CN1C=CC(=N1)C2=CC(=C(C=C2)C#N)Cl)NC(=O)C3=NNC(=C3)C(C)O

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO 74 mg/mL (185.53 mM)
Water Insoluble
Ethanol Warmed: 35 mg/mL

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Moilanen AM, Riikonen R, Oksala R, et al. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies Scientific reports (2015). PMID: 26137992 DOI: 10.1038/srep12007 Source material
  2. [2] Sugawara T, Baumgart SJ, Nevedomskaya E, et al. Darolutamide is a potent androgen receptor antagonist with strong efficacy in prostate cancer models International journal of cancer (2019). PMID: 30828788 DOI: 10.1002/ijc.32242 Source material
  3. [3] Afshan S, Kim YG, Mattsson J, et al. Targeting the cancer cells and cancer-associated fibroblasts with next-generation FGFR inhibitors in prostate cancer co-culture models Cancer medicine (2024). PMID: 39300962 DOI: 10.1002/cam4.70240 Source material

Publications

1 publication citing this product

  1. Syeda Afshan, .et al. , Cancer Med, 2024, Sep;13(18):e70240 PMID: 39300962

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