NPASS Compound

Natural Product: NPC74751

Natural Product ID	NPC74751
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Acetoxolone
IUPAC Name	(2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-10-acetyloxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid
Synonyms	Acetoxolone
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL207413
PubChem CID	94320
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 85 89 0 0 0 0 0 0 0 0999 V2000 8.3950 -1.2532 -1.7792 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0235 -0.7526 -2.0585 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8489 -0.0915 -3.1191 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9474 -0.9623 -1.2438 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6311 -0.4850 -1.5066 C 0 0 1 0 0 0 0 0 0 0 0 0 3.7699 -1.6712 -1.7553 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2965 -1.3839 -1.6083 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0576 -0.9335 -0.1537 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7733 0.3748 -0.0306 C 0 0 2 0 0 0 0 0 0 0 0 0 4.2063 0.3988 -0.3794 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4873 1.8390 -0.8647 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1386 0.1991 0.8134 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5419 0.8470 1.3946 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0928 1.2961 1.4697 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1536 0.1861 1.1065 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6016 -0.6736 -0.0301 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2287 -1.9050 0.0378 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2226 -3.0684 -0.1090 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6466 -1.6593 0.2945 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1099 -0.4469 0.6065 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2283 0.7316 0.7147 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0989 1.3985 -0.6538 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7317 1.7657 1.6760 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0657 1.5096 2.2690 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0830 0.8843 1.3608 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5994 -0.4082 0.8393 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3546 -1.0066 -0.2953 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1713 -0.0767 -1.1164 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.0537 -0.4613 -2.5989 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7862 1.3622 -1.0177 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5940 1.8708 0.3619 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6414 -0.1795 -0.8148 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2932 0.8114 -0.3955 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3467 -1.3634 -0.9826 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2788 0.5720 2.2858 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1069 -0.6097 2.3765 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6023 -2.0323 0.6796 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9619 -0.4431 -1.2790 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9358 -1.4876 -2.7209 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3464 -2.1837 -1.1543 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7190 0.0664 -2.4901 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0821 -2.5356 -1.1138 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9157 -2.0287 -2.7980 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0686 -0.5202 -2.2692 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7336 -2.2850 -1.8513 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1966 1.1039 -0.6744 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7052 2.4889 0.0266 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3937 1.8656 -1.4969 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6145 2.2664 -1.3642 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8742 1.0324 0.9273 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7901 -0.7096 0.6572 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6029 0.1376 1.7673 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2035 1.6642 1.6910 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6018 -0.0358 2.0988 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9622 1.5641 2.5620 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0079 2.1947 0.8484 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2809 -0.1690 -0.9784 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3051 -2.5350 0.2145 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7642 2.3125 -0.6796 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4683 0.7538 -1.4726 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0869 1.8166 -0.8264 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7649 2.7908 1.1976 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0294 1.9266 2.5482 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0339 0.9428 3.2460 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5051 2.5043 2.5825 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7041 -1.1502 1.6964 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0431 -1.8182 0.0566 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6315 -1.5318 -0.9649 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1091 -0.0979 -3.0307 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9524 -0.1499 -3.1640 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0320 -1.5779 -2.6059 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8327 1.5368 -1.5962 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6236 1.9492 -1.4967 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5615 2.3520 0.6942 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8895 2.7523 0.3189 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3249 -1.3530 -1.2933 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0136 1.4000 2.2641 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9128 0.3564 3.3198 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7490 -0.3631 1.9349 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1131 -1.6866 2.2225 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0493 -0.3387 2.8756 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7007 -0.4093 3.1406 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5420 -3.0269 0.1466 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1916 -2.0988 1.7000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6976 -1.8660 0.8096 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 10 12 1 0 9 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 2 0 20 21 1 0 21 22 1 6 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 6 28 30 1 0 30 31 1 0 28 32 1 0 32 33 2 0 32 34 1 0 25 35 1 1 15 36 1 1 8 37 1 1 10 5 1 0 21 15 1 0 31 25 1 0 16 8 1 0 26 20 1 0 1 38 1 0 1 39 1 0 1 40 1 0 5 41 1 6 6 42 1 0 6 43 1 0 7 44 1 0 7 45 1 0 9 46 1 6 11 47 1 0 11 48 1 0 11 49 1 0 12 50 1 0 12 51 1 0 12 52 1 0 13 53 1 0 13 54 1 0 14 55 1 0 14 56 1 0 16 57 1 6 19 58 1 0 22 59 1 0 22 60 1 0 22 61 1 0 23 62 1 0 23 63 1 0 24 64 1 0 24 65 1 0 26 66 1 1 27 67 1 0 27 68 1 0 29 69 1 0 29 70 1 0 29 71 1 0 30 72 1 0 30 73 1 0 31 74 1 0 31 75 1 0 34 76 1 0 35 77 1 0 35 78 1 0 35 79 1 0 36 80 1 0 36 81 1 0 36 82 1 0 37 83 1 0 37 84 1 0 37 85 1 0 M END

Standard InCHIKey	FTQDJVZNPJRVPG-XWEVEMRCSA-N
Standard InCHI	InChI=1S/C32H48O5/c1-19(33)37-24-10-11-30(6)23(27(24,2)3)9-12-32(8)25(30)22(34)17-20-21-18-29(5,26(35)36)14-13-28(21,4)15-16-31(20,32)7/h17,21,23-25H,9-16,18H2,1-8H3,(H,35,36)/t21-,23-,24-,25+,28+,29-,30-,31+,32+/m0/s1
SMILES	CC(=O)O[C@H]1CC[C@]2([C@H](C1(C)C)CC[C@@]1([C@@H]2C(=O)C=C2[C@@]1(C)CC[C@@]1([C@H]2C[C@](C)(CC1)C(=O)O)C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	512.35	Volume:	552.651 ? Van der Waals volume.
Dense:	0.927	LogP:	2.971 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.793 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.831 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	29.0
TPSA:	80.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.404	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.794	Fsp³:	0.844
MCE-18:	108.407 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.748	Fluc inhibitor:	0.007 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.069 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.393	Promiscuous compounds:	0.343

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.92	MDCK Permeability:	-4.671
Pgp-inhibitor:	0.093	Pgp-substrate:	0.027
PAMPA:	0.996 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.0
20% Bioavailability (F20%):	0.948	30% Bioavailability (F30%):	0.335
50% Bioavailability (F50%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.978
Plasma Protein Binding (PPB):	89.475%	Volume Distribution (VD):	-0.47
Fu:	9.558% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.995
OATP1B3 inhibitor:	0.0	BCRP inhibitor:	0.002
BSEP inhibitor:	0.976

ADMET: Metabolism

CYP1A2-inhibitor:	0.005	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.02	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.003
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.983
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.488
HLM stability:	0.012 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

1.51

Half-life (T1/2):

1.204

ADMET: Toxicity

hERG Blockers:	0.013	hERG Blockers (10um):	0.048
Human Hepatotoxicity (H-HT):	0.67	Drug-induced Liver Injury (DILI):	0.518
AMES Toxicity:	0.099	Rat Oral Acute Toxicity:	0.298
Maximum Recommended Daily Dose:	0.409	Skin Sensitization:	0.994
Carcinogencity:	0.817	Eye Corrosion:	0.289
Eye Irritation:	0.824	Respiratory Toxicity:	0.501
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.258
Hematotoxicity:	0.442	Drug-induced Nephrotoxicity:	0.945
Genotoxicity:	0.917	RPMI-8226 Immunitoxicity:	0.045
A549 Cytotoxicity:	0.039	Hek293 Cytotoxicity:	0.14
BCF:	1.064 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.07 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.911 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.197 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1007/s11164-015-2099-x]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1134/S1021443711030101]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[16441081]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16675659]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22074222]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[22074222]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[23867078]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[23867078]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24479468]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	roots	n.a.	n.a.	PMID[24957203]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25445757]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25744461]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26841168]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32196343]
NPO10026	Mitracarpus scaber	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23019	Glycyrrhiza kansuensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7786	Lentinus tigrinus	Species	Lentinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23019	Glycyrrhiza kansuensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23019	Glycyrrhiza kansuensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23019	Glycyrrhiza kansuensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7786	Lentinus tigrinus	Species	Lentinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10026	Mitracarpus scaber	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	16
Activity	3
Inhibition	5
Ratio IC50	3
Ratio CC50/IC50	1

Activity Type	# Activity
Individual protein	19
Organism	4
Others	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1137	Individual protein	11-beta-hydroxysteroid dehydrogenase 1	Homo sapiens	IC50	=	800.0	nM	PMID[16759088]
NPT1137	Individual protein	11-beta-hydroxysteroid dehydrogenase 1	Homo sapiens	Activity	>	70.0	%	PMID[16759088]
NPT1587	Individual protein	Estradiol 17-beta-dehydrogenase 1	Homo sapiens	IC50	=	18800.0	nM	PMID[16759088]
NPT1137	Individual protein	11-beta-hydroxysteroid dehydrogenase 1	Homo sapiens	IC50	=	3450.0	nM	PMID[16759088]
NPT1138	Individual protein	11-beta-hydroxysteroid dehydrogenase 2	Homo sapiens	IC50	=	201.0	nM	PMID[16759088]
NPT1588	Individual protein	Estradiol 17-beta-dehydrogenase 2	Homo sapiens	IC50	=	3780.0	nM	PMID[16759088]
NPT1138	Individual protein	11-beta-hydroxysteroid dehydrogenase 2	Homo sapiens	IC50	=	6430.0	nM	PMID[16759088]
NPT1138	Individual protein	11-beta-hydroxysteroid dehydrogenase 2	Homo sapiens	Inhibition	=	85.7	%	PMID[19914836]
NPT1137	Individual protein	11-beta-hydroxysteroid dehydrogenase 1	Homo sapiens	Inhibition	=	47.1	%	PMID[19914836]
NPT1137	Individual protein	11-beta-hydroxysteroid dehydrogenase 1	Homo sapiens	Activity	=	53.0	%	PMID[20851614]
NPT1138	Individual protein	11-beta-hydroxysteroid dehydrogenase 2	Homo sapiens	Activity	=	14.0	%	PMID[20851614]
NPT1138	Individual protein	11-beta-hydroxysteroid dehydrogenase 2	Homo sapiens	IC50	=	750.0	nM	PMID[21376605]
NPT1137	Individual protein	11-beta-hydroxysteroid dehydrogenase 1	Homo sapiens	IC50	=	7138.0	nM	PMID[20851614]
NPT1137	Individual protein	11-beta-hydroxysteroid dehydrogenase 1	Homo sapiens	Inhibition	=	12.0	%	PMID[21376605]
NPT1137	Individual protein	11-beta-hydroxysteroid dehydrogenase 1	Homo sapiens	IC50	=	7100.0	nM	PMID[21376605]
NPT1138	Individual protein	11-beta-hydroxysteroid dehydrogenase 2	Homo sapiens	Inhibition	=	14.0	%	PMID[21376605]
NPT203	Individual protein	Carboxylesterase 2	Homo sapiens	IC50	=	40510.0	nM	PMID[26900660]
NPT166	Individual protein	Acyl coenzyme A:cholesterol acyltransferase	Homo sapiens	IC50	=	49860.0	nM	PMID[26900660]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT138	Organism	Brugia malayi	Brugia malayi	Inhibition	=	9.45	%	PMID[23541646]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	IC50	=	1001500.0	nM	PMID[22520261]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	IC50	>	517870.0	nM	PMID[22520261]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	IC50	=	121140.0	nM	PMID[22520261]
NPT2	Others	Unspecified	n.a.	IC50	>	40000.0	nM	PMID[18562200]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	10.0	n.a.	PMID[21376605]
NPT2	Others	Unspecified	n.a.	Ratio CC50/IC50	=	4.3	n.a.	PMID[22520261]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	1.2	n.a.	PMID[26900660]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference
-	Brugia malayi	LC100	>	100.0	uM	PMID[23541646]

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC74751 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	21984
0.1-0.2	23729
0.2-0.3	3604
0.3-0.4	404
0.4-0.5	91
0.5-0.6	21
0.6-0.7	11
0.7-0.8	1
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8485	Intermediate Similarity	NPC482712
0.7206	Intermediate Similarity	NPC96095
0.7143	Intermediate Similarity	NPC4036
0.7143	Intermediate Similarity	NPC65120
0.7143	Intermediate Similarity	NPC145067
0.7143	Intermediate Similarity	NPC233455
0.7143	Intermediate Similarity	NPC158030
0.7121	Intermediate Similarity	NPC480944
0.7	Intermediate Similarity	NPC471967
0.6829	Remote Similarity	NPC482752
0.6806	Remote Similarity	NPC608622
0.6264	Remote Similarity	NPC471965
0.6264	Remote Similarity	NPC482749
0.6222	Remote Similarity	NPC482747
0.6222	Remote Similarity	NPC202666
0.6222	Remote Similarity	NPC471961
0.6222	Remote Similarity	NPC482746
0.6222	Remote Similarity	NPC242015
0.6022	Remote Similarity	NPC14617
0.6	Remote Similarity	NPC262199
0.5714	Remote Similarity	NPC78580
0.5638	Remote Similarity	NPC482741
0.5638	Remote Similarity	NPC482745
0.5638	Remote Similarity	NPC482743
0.5638	Remote Similarity	NPC146753
0.5443	Remote Similarity	NPC198818
0.5408	Remote Similarity	NPC482734
0.5408	Remote Similarity	NPC182342
0.5408	Remote Similarity	NPC482727
0.5408	Remote Similarity	NPC471964
0.5395	Remote Similarity	NPC263272
0.5385	Remote Similarity	NPC482711
0.5385	Remote Similarity	NPC26413
0.5309	Remote Similarity	NPC169343
0.5294	Remote Similarity	NPC476878
0.5248	Remote Similarity	NPC482737
0.5248	Remote Similarity	NPC482735
0.519	Remote Similarity	NPC281524
0.519	Remote Similarity	NPC474525
0.5063	Remote Similarity	NPC120840
0.5063	Remote Similarity	NPC104545

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC74751 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6209
0.1-0.2	2879
0.2-0.3	53
0.3-0.4	2
0.4-0.5	1
0.5-0.6	0
0.6-0.7	3
0.7-0.8	1
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD7748	Pre-clinical
0.8676	High Similarity	NPD7902	Phase 4
0.7143	Intermediate Similarity	NPD7515	Phase 2
0.68	Remote Similarity	NPD7900	Approved
0.68	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6222	Remote Similarity	NPD8328	Phase 2

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data