Panobinostat sensitivity varied across thoracic cancer cells. H69 SCLC cells had an IC50 of 20 nmol/L and an LD50 of 25 nmol/L, whereas the H661 NSCLC IC50 exceeded 800 nmol/L. The study distinguished growth inhibition relative to vehicle from loss of initially plated cells. [2]
Panobinostat combined with pomalidomide produced ZIP-defined synergy in OPM2, MM.1S and KMS12PE myeloma cells, but not U266B1. CRBN knockdown largely removed synergy in OPM2. These 96-hour viability results are specific to the combination and model. [3]
Biochemical HDAC inhibition comparison
Biochemical assay · A2780-derived immunoprecipitated HDAC1 complexes and human recombinant HDAC8 [1]
Panobinostat inhibited both preparations, with different IC50 values. These are assay endpoints, not treatment doses.
Literature-Reported Treatment Conditions
- Exposure duration
- HDAC1: 10 min inhibitor preincubation, then 45 min substrate reaction; HDAC8 duration not specified in the read methods.
- Method
- Radiolabeled acetyl-H4 deacetylation for HDAC1; commercial colorimetric/fluorimetric HDAC8 assay.
- Vehicle
- DMSO stocks; final enzyme-assay DMSO fraction not specified.
- Reported limits
- Tested concentration grid and final enzyme-assay vehicle fraction not specified; HDAC8 incubation duration not specified.
Methods and source locations
Compound reported in the paper: Panobinostat (LBH589)
Evidence applies to the reported panobinostat material and experimental conditions; salt equivalence, current Adooq lot performance and clinical efficacy are not established.
Table 1 (panobinostat row and footnote); Methods: Compounds; Histone deacetylase activity assays
Inhibition of immunoprecipitated HDAC1 activity: Mean±SD; three independent experiments on a single lysate, per assay methods and Table 1 footnote. — Table 1, Panobinostat / HDAC1-IP Ac-H4; Methods: Histone deacetylase activity assays
Inhibition of recombinant HDAC8 activity: Table 1 reports average IC50±SD for three independent experiments; commercial HDAC8 assay. — Table 1, Panobinostat / HDAC8 and footnote
Thoracic cancer cell sensitivity panel
Cell-based study · 37 human/mouse NSCLC, mesothelioma and SCLC cell lines [2]
Responses varied substantially: H69 IC50/LD50 were 20/25 nmol/L, while H661 IC50 was >800 nmol/L. LD50 was calibrated against initially plated cells and differs from IC50.
Literature-Reported Treatment Conditions
- Treatment concentration
- 0–800 nmol/L
- Exposure duration
- 48 and 72 h readings; Table 1 does not assign each value to a specific read time.
- Method
- Continuous exposure; tetrazolium viability assay in quadruplicate with standard cell-number curve; repeated assays.
- Vehicle
- Vehicle-treated comparator; material supplied in 5% dextrose suspension; final cellular vehicle composition not specified.
- Reported limits
- Table 1 gives no error estimates, exact independent repeat count, or per-value read time.
Methods and source locations
Compound reported in the paper: Panobinostat (LBH589)
Evidence applies to the reported panobinostat material and experimental conditions; salt equivalence, current Adooq lot performance and clinical efficacy are not established.
Table 1 and cellular Results; Methods: Reagents; Cell Proliferation MTS Assays
H69 growth inhibition relative to vehicle-treated cells: Tetrazolium assay; the paper defines IC50 as 50% growth inhibition versus vehicle. — Table 1, human SCLC H69 row; Cell Proliferation MTS Assays
H69 loss of initially plated cells: Cell-number-calibrated tetrazolium assay; paper defines LD50 as killing 50% of initially plated cells. — Table 1, human SCLC H69 row; Cell Proliferation MTS Assays
H661 growth inhibition relative to vehicle: Limited sensitivity within tested concentration range. — Table 1, human NSCLC H661 row
Cell-line-dependent pomalidomide–panobinostat interaction
Cell-based study · OPM2, MM.1S, U266B1 and intrinsically IMiD-resistant KMS12PE myeloma cells; OPM2 control and two CRBN-knockdown lines [3]
ZIP synergy was observed in OPM2, MM.1S and KMS12PE, but not U266B1. OPM2 synergy was largely lost after CRBN knockdown; this is a combination effect.
Literature-Reported Treatment Conditions
- Treatment concentration
- 6×6 dose matrices: panobinostat 0–100 nM and pomalidomide 0–10,000 nM (Figure 1 axes).
- Exposure duration
- 96 h (4 days)
- Method
- CellTiter-Glo relative viability normalized to vehicle; ZIP interaction analysis. Figure 1: three independent experiments; Methods: triplicate wells.
- Vehicle
- DMSO; final vehicle percentage not specified.
- Co-treatment
- Pomalidomide plus panobinostat; single-agent matrices and empty-vector/CRBN-knockdown controls.
- Reported limits
- Final DMSO fraction not specified. No clinical or animal efficacy is inferred.
Methods and source locations
Compound reported in the paper: Panobinostat (LBH589); Compound label in the paper: A10518 (AdooQ Bioscience; author-reported)
Evidence applies to the reported panobinostat material and experimental conditions; salt equivalence, current Adooq lot performance and clinical efficacy are not established.
Figure 1 A-C and caption; Results Sec3; Methods Sec11–13, Sec15
Interaction in cell viability across drug dose matrices: ZIP positive scores indicate synergy relative to the model non-interaction surface; no exact score transcribed from the image. — Figure 1 A-C; Results Sec3; Analysis of synergy scores
