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Table 2 Efficacy of drugs in NF-κB, MMP-13, and bone remodeling assays

From: Randomized controlled studies on the efficacy of antiarthritic agents in inhibiting cartilage degeneration and pain associated with progression of osteoarthritis in the rat

Drug

Test range (μM)

Overlapping effective and nontoxic rangea (μM)

NF-κB

MMP-13

Bone

Tested in vivo

Alendronate

0.625–40

Bone control

N/A

NE

1.25 and 20 μΜb

MMT/MCLT

Amrinone

0.625–80

80

NE

80

NE

No

Ascomycin

0.01–40

1.25–40

E

NE

E

TBD

BAY-117082

0.188–192

6–192

NE

E

E

Proprietary

BMS-345541

0.24–15.6

0.244

NE

E

E

Proprietary

Boswellic acid

0.61–680

40–680

E

E

E

Purity an issue

Clonidine

0.156–100

10–100

NE

NE

E

MMT/MCLT and MIA

CORM-2

0.625–40

20–40+

N/A

E

E

Proprietary

Curcumin

0.84–108

13.5–54

E

E

E

MMT/MCLT and MIA

Curcumin-14

1.25–80

2.5–10

E

E

NE

TBD

Diacerein

1.5–217

Toxic to chondrocytes

E

E

E

Toxicity and purity issues

EGCG

0.688–44

5.5–44

E

E

NE

Purity an issue

Fluocinolonec

0.010–100

3.1–100

E

E

E

MMT/MCLT and MIA

GM6001

0.33–25

NA

NA

25

NE

No

NF-κB activation inhibitor IV

0.156–10

NA

7.7

NE

N/A

No

IKK inhibitor Vd (IMMD-0354)

0.025–26

1.625–26

 

E

E

Cost-prohibitive/proprietary

IKK inhibitor VI

0.028–15.2

0.24–15.2

E

E

E

Cost-prohibitive/proprietary

IKK inhibitor VIII (ACHP)

0.25–16

4 (toxicity to synovial cells)

N/A

E

E

Cost-prohibitive/proprietary

Meloxicam

0.125–32

16–32

E

NE

NE

MIA

Pimecrolimus (ELIDEL; Meda Pharma, Luxembourg)

0.625–40

2.5–20

E

NE

E

TBD

Resveratrol

3.125–200

6.25–200

NE

E

E

TBD

Rhein

0.625– 40

N/A

NE

E

NE

Lack of potency

SC514

0.125–32

NE in nontoxic range

NE

NE

NE

Proprietary

Sulfasalazined

12.5–1600

150–1600

 

E

E

Lack of potency

Sulindac

4.35–280

280

E

E

E

Lack of potency

Tacrolimuse (FK506)

0.813–100

50

E

E

E

MMT/MCLT and MIA

Tranilast

0.125–8

1–8

NE

E

E

MIA

Triamcinolone acetonide

0.7–2000

250–500

E

E

E

Aristospan (TH) tested instead

Triamcinolone hexacetonidee

3.125–3750

62.5–3750

E

E

E

MMT/MCLT and MIA

Withaferin Af

0.25–17

4.25–17

E

E

E

MMT/MCLT model

  1. ACHP 2-amino-6-(2-(cyclopropylmethoxy)-6-hydroxyphenyl)-4-(4-piperidinyl)-3-pyridinecarbonitrile, E effective nontoxic concentration that overlaps with other tested agents, EGCG epigallocatechin gallate, FK506 tacrolimus, IKK inhibitor of nuclear factor κB kinase, MIA monoiodoacetic acid, MMP matrix metalloproteinase, MMT/MCLT medial meniscal tear/medial collateral ligament tear, N/A not applicable, NF-κB nuclear factor κ-light-chain-enhancer of activated B cells, NE not effective and nontoxic within the effective/nontoxic range for the other tested drugs, SC514 selective reversible inhibitor of inhibitor of nuclear factor κB kinase 2, TBD to be determined, TH triamcinolone hexacetonide
  2. The overlapping dose range that was effective and nontoxic is also shown. If effective in vitro, it is noted whether in vivo testing occurred and in which models. See Figs. 1, 2 and 3 and Additional file 1 for results in the specific assays
  3. aDose found to inhibit with minimal or no toxicity to synovium or cartilage. Values reflect overlapping range if agent was effective in more than one assay
  4. bUsed as a bone remodeling control; not tested <1.25 μM in the bone assay
  5. cFluocinolone was effective at much lower doses in both the bone and MMP-13 assays
  6. dEffective in the MMP-13 and bone assays; at higher concentrations, this compound blocked NF-κB activity in the HeLa assay but also blocked expression of the Renilla plasmid luciferase. At lower concentrations, it was not effective against NF-κB
  7. eTacrolimus and TH were effective at much lower doses in the bone assay. For TH, lower doses may have been effective in the NF-κB assay but were not tested
  8. fBecause of the promising results, especially in the bone and MMP-13 assays, and in spite of its slight toxicity in the synovial and chondrocyte assays, Withaferin A was tested in the MMT/MCLT model