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Fig. 1 · Structure
Cat. No.
A11195
CAS No.
819812-04-9
Formula
C30H42N2O9
Mol. Weight
574.66

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KW-2478

Cat. No. A11195 CAS 819812-04-9

HSP90 inhibitor

KW-2478 is an agent that targets the human heat-shock protein 90 (Hsp90) with potential antineoplastic activity.

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Publications for KW-2478

1 publication citing this product

  1. Hiroki Murano, .et al. , Plant Biotechnol Rep, 2017, 11:107-113
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Biological Activity

Bioactivity / Mechanism

KW-2478 reduced HSP90α–BCR/ABL co-immunoprecipitation in K562/G01 CML cells after 48 h at 2 µM, consistent with interference with Hsp90 chaperone function. This cellular result does not establish biochemical affinity or isoform selectivity; reduced client abundance may contribute to the co-IP change. [1]

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

Target & Activity

Target Activity Value
HSP90 3.8 nM

In Vitro Studies

KW-2478 inhibited CML-cell viability in a time-dependent assay. At 48 h, reported IC50 values were 5.195 µM in K562 cells and 1.424 µM in K562/G01 cells; at 72 h they were 4.659 and 0.867 µM, respectively. [1]

In ten primary myeloma samples co-cultured with HS-5 stromal cells for 48 h, KW-2478 enhanced bortezomib activity in three of four tested combinations. The 1 µmol/l KW-2478 plus 3 nmol/l bortezomib comparison was not significant, and some individual samples showed no additional response. [2]

Disruption of HSP90α–BCR/ABL association in CML cells

Cell-based study · K562/G01 human CML cells, described as imatinib-resistant with BCR/ABL amplification [1]

Reciprocal co-immunoprecipitation detected HSP90α–BCR/ABL association without treatment and reduced association after KW-2478. Input and IgG controls are shown. This supports a cellular chaperone mechanism; it does not measure binding affinity, ATP competition or isoform selectivity.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
HSP90α–BCR/ABL co-immunoprecipitationQualitative association Reduced after KW-2478 compared with no KW-2478 treatment[1]

Literature-Reported Treatment Conditions

Treatment concentration
2 µM
Exposure duration
48 h
Method
Incubation followed by reciprocal co-IP and western blotting
Vehicle
DMSO used to dissolve KW-2478; final fraction not stated
Reported limits
Co-IP-specific biological replicate count and final DMSO fraction are not specified in the acquired method/caption.
Methods and source locations

Compound reported in the paper: KW-2478; Compound label in the paper: KW-2478 (KW)

Results apply to the paper’s named KW-2478 material and stated models; no equivalence to an Adooq lot or unreported salt/hydrate is established.

Methods: Reagents and antibodies; Coimmunoprecipitation; Results: KW-2478 inhibits the chaperone function of HSP90; Fig. 5e–f

HSP90α–BCR/ABL co-immunoprecipitation: Reciprocal IP with anti-BCR/ABL or anti-HSP90α; western blot; input and IgG controls — Fig. 5e–f; Coimmunoprecipitation method

Time-dependent KW-2478 viability responses in CML cell lines

Cell-based study · K562 and K562/G01 human CML cells [1]

CCK-8 viability assays reported lower IC50 values in K562/G01 than K562 at 48 and 72 h. These are cellular assay endpoints, not biochemical Hsp90 IC50 values or universal treatment concentrations.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
K562 viability inhibitionIC50 48 h: 5.195 µM; 72 h: 4.659 µM[1]
K562/G01 viability inhibitionIC50 48 h: 1.424 µM; 72 h: 0.867 µM[1]

Literature-Reported Treatment Conditions

Treatment concentration
Increasing concentration series; Fig. 1a axis spans 0.001–10 µM; exact complete point list not tabulated
Exposure duration
48 and 72 h endpoints adopted; 24 h also tested
Method
CCK-8 assay, absorbance at 450 nm; IC50 fitted using GraphPad Prism 8
Vehicle
DMSO stock; final fraction not stated
Reported limits
IC50 uncertainty intervals and complete numeric dose/response data not provided for Fig. 1a. Figure caption describes values as mean standard deviation of three independent experiments; no IC50 ± uncertainty is given.
Methods and source locations

Compound reported in the paper: KW-2478; Compound label in the paper: KW-2478 (KW)

Results apply to the paper’s named KW-2478 material and stated models; no equivalence to an Adooq lot or unreported salt/hydrate is established.

Methods: Cell viability assay; Results first subsection; Fig. 1a

K562 viability inhibition: CCK-8, fitted concentration response — Fig. 1a labels; Results first subsection

K562/G01 viability inhibition: CCK-8, fitted concentration response — Fig. 1a labels; Results first subsection

KW-2478 plus bortezomib in primary myeloma co-culture

Cell-based study · Ten primary human relapsed multiple-myeloma samples co-cultured with HS-5 stromal cells [2]

KW-2478 at 1 or 2 µmol/l enhanced the effect of bortezomib in three of four tested combinations. Responses varied among samples; the 1 µmol/l KW-2478 plus 3 nmol/l bortezomib comparison was not significant.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Primary MM cell viability, combination versus same bortezomib concentrationPaired comparison KW 1 µmol/l + BTZ 3 nmol/l: NS; KW 2 + BTZ 3: P<0.05; KW 1 + BTZ 6: P<0.05; KW 2 + BTZ 6: P<0.01[2]

Literature-Reported Treatment Conditions

Treatment concentration
KW-2478: 1 and 2 µmol/l; bortezomib: 3 and 6 nmol/l
Exposure duration
48 h
Method
Continuous drug exposure in HS-5 co-culture; Guava Via Count viability assay
Vehicle
Both compounds dissolved in DMSO and diluted in culture medium; final DMSO fraction not stated
Co-treatment
Bortezomib; single-agent KW-2478 and matched single-agent bortezomib comparisons
Reported limits
No numerical mean viability percentages tabulated for Fig. 3; untreated normalization and a separate matched DMSO control are not detailed in the patient-assay subsection.
Methods and source locations

Compound reported in the paper: KW-2478; Compound label in the paper: KW-2478 (KW)

Results apply to the paper’s named KW-2478 material and stated models; no equivalence to an Adooq lot or unreported salt/hydrate is established.

Reagents; Measurement of drug activity in primary MM cells; Results: Cytotoxicity in MM patient samples; Fig. 3

Primary MM cell viability, combination versus same bortezomib concentration: Guava Via Count; paired t-test, n=10 patient samples; units as specified in treatment — Fig. 3 significance brackets; Results: Cytotoxicity in MM patient samples

In Vivo Studies

In an OPM-2/GFP orthotopic SCID mouse model, twice-weekly KW-2478 plus bortezomib reduced fluorescence compared with monotherapy groups. KW-2478 alone at 100 or 200 mg/kg did not significantly reduce fluorescence. The 200 mg/kg KW-2478 combination lowered serum M protein versus bortezomib alone (P<0.05; n=5/group). [2]

KW-2478 plus bortezomib in orthotopic myeloma

Animal study · SCID mice with OPM-2/GFP human myeloma lesions; six groups of five mice balanced by baseline serum M protein [2]

With twice-weekly treatment, KW-2478 monotherapy at 100 or 200 mg/kg did not significantly reduce GFP fluorescence. Combination groups showed reduced fluorescence; the 200 mg/kg KW-2478 combination also significantly reduced serum M protein compared with bortezomib alone. These results are regimen-specific.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
GFP fluorescence as tumor-burden readout on day 50Qualitative fluorescence comparison No significant decrease reported with either KW-2478 monotherapy dose; clear decreases reported in combination groups[2]
Serum M protein (Igλ) on day 40Between-group comparison KW-2478 200 mg/kg + BTZ 0.3 mg/kg versus BTZ alone: P<0.05[2]

Conditions shared by the study groups

Vehicle
Saline
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
Saline controlSaline and matched monotherapy groupsReference fluorescence and serum M protein group.[2]
KW-2478 monotherapy, 100 mg/kg
KW-2478 100 mg/kg		Saline and matched monotherapy groupsNo significant decrease in GFP fluorescence reported versus control.[2]
KW-2478 monotherapy, 200 mg/kg
KW-2478 200 mg/kg		Saline and matched monotherapy groupsNo significant decrease in GFP fluorescence reported versus control.[2]
Bortezomib monotherapy
Bortezomib 0.3 mg/kg		Saline and matched monotherapy groupsSmall decrease in GFP-fluorescent lesions reported; comparator for combination.[2]
KW-2478 100 mg/kg plus bortezomib
KW-2478 100 mg/kg + bortezomib 0.3 mg/kg		Saline and matched monotherapy groupsClear fluorescence decrease reported; lower M protein, without significance asserted versus BTZ alone.[2]
KW-2478 200 mg/kg plus bortezomib
KW-2478 200 mg/kg + bortezomib 0.3 mg/kg		Saline and matched monotherapy groupsClear fluorescence decrease reported; serum M protein lower than BTZ alone (P<0.05).[2]
Saline control
Model: OPM-2/GFP orthotopic SCID mouse model; n=5/group
Treatment course: Control follow-up: serum M protein day 40 and fluorescence imaging day 50
Reported limits: Sex, age and specific SCID strain unavailable in acquired orthotopic methods; saline volume not specified. Control injection volume, timing and route not explicitly specified.
KW-2478 monotherapy, 100 mg/kg
Model: OPM-2/GFP orthotopic SCID mouse model; n=5/group
Route: Intravenous
Frequency: Twice weekly
Treatment course: Four administrations on days 27, 30, 34 and 37 after tumor-cell inoculation; serum M protein day 40; imaging day 50
Reported limits: Sex, age and specific SCID strain unavailable in acquired orthotopic methods; saline volume not specified.
KW-2478 monotherapy, 200 mg/kg
Model: OPM-2/GFP orthotopic SCID mouse model; n=5/group
Route: Intravenous
Frequency: Twice weekly
Treatment course: Four administrations on days 27, 30, 34 and 37 after tumor-cell inoculation; serum M protein day 40; imaging day 50
Reported limits: Sex, age and specific SCID strain unavailable in acquired orthotopic methods; saline volume not specified.
Bortezomib monotherapy
Model: OPM-2/GFP orthotopic SCID mouse model; n=5/group
Route: Intravenous
Frequency: Twice weekly
Treatment course: Four administrations on days 27, 30, 34 and 37 after tumor-cell inoculation; serum M protein day 40; imaging day 50
Reported limits: Sex, age and specific SCID strain unavailable in acquired orthotopic methods; saline volume not specified.
KW-2478 100 mg/kg plus bortezomib
Model: OPM-2/GFP orthotopic SCID mouse model; n=5/group
Route: Intravenous
Frequency: Twice weekly
Treatment course: Four administrations on days 27, 30, 34 and 37 after tumor-cell inoculation; serum M protein day 40; imaging day 50
Reported limits: Sex, age and specific SCID strain unavailable in acquired orthotopic methods; saline volume not specified.
KW-2478 200 mg/kg plus bortezomib
Model: OPM-2/GFP orthotopic SCID mouse model; n=5/group
Route: Intravenous
Frequency: Twice weekly
Treatment course: Four administrations on days 27, 30, 34 and 37 after tumor-cell inoculation; serum M protein day 40; imaging day 50
Reported limits: Sex, age and specific SCID strain unavailable in acquired orthotopic methods; saline volume not specified.
Methods and source locations

Compound reported in the paper: KW-2478; Compound label in the paper: KW-2478 (KW)

Results apply to the paper’s named KW-2478 material and stated models; no equivalence to an Adooq lot or unreported salt/hydrate is established.

Reagents; Anti-tumor activity in OPM-2/GFP orthotopic model; Statistical methods: Serum M protein; corresponding Results; Fig. 6b–c

GFP fluorescence as tumor-burden readout on day 50: Whole-body fluorescence imaging; five mice/group; no numerical effect size inferred — Fig. 6b; corresponding Results

Serum M protein (Igλ) on day 40: ELISA; n=5/group; displayed mean+s.d.; one-way ANOVA followed by Tukey test — Fig. 6c; Statistical methods: Serum M protein; corresponding Results

Saline control · Methods: Anti-tumor activity in OPM-2/GFP orthotopic model; Fig. 6b–c; corresponding Results

KW-2478 monotherapy, 100 mg/kg · Methods: Anti-tumor activity in OPM-2/GFP orthotopic model; Fig. 6b–c; corresponding Results

KW-2478 monotherapy, 200 mg/kg · Methods: Anti-tumor activity in OPM-2/GFP orthotopic model; Fig. 6b–c; corresponding Results

Bortezomib monotherapy · Methods: Anti-tumor activity in OPM-2/GFP orthotopic model; Fig. 6b–c; corresponding Results

KW-2478 100 mg/kg plus bortezomib · Methods: Anti-tumor activity in OPM-2/GFP orthotopic model; Fig. 6b–c; corresponding Results

KW-2478 200 mg/kg plus bortezomib · Methods: Anti-tumor activity in OPM-2/GFP orthotopic model; Fig. 6b–c; corresponding Results

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 819812-04-9
Applications HSP90 inhibitor
Formula C30H42N2O9
Molecular Weight 574.66
SMILES
CCC1=C(C=C(C(=C1CC(=O)N(CCOC)CCOC)C(=O)C2=CC(=C(C=C2)OCCN3CCOCC3)OC)O)O

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO 114 mg/mL (198.37 mM)
Water Insoluble
Ethanol 3 mg/mL (5.22 mM)

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.

In Vivo Preparation

Concentration
9 mg/mL
Vehicle
30% propylene glycol, 5% Tween 80, 65% D5W

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] Dachuan Zeng, Miao Gao, Renren Zheng, et al. The HSP90 inhibitor KW-2478 depletes the malignancy of BCR/ABL and overcomes the imatinib-resistance caused by BCR/ABL amplification Experimental Hematology & Oncology (2022). PMID: 35624462 DOI: 10.1186/s40164-022-00287-w Source material
  2. [2] T Ishii, T Seike, T Nakashima, et al. Anti-tumor activity against multiple myeloma by combination of KW-2478, an Hsp90 inhibitor, with bortezomib Blood Cancer Journal (2012). PMID: 22829970 DOI: 10.1038/bcj.2012.13 Source material

Publications

1 publication citing this product

  1. Hiroki Murano, .et al. , Plant Biotechnol Rep, 2017, 11:107-113

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