NPASS Compound

Natural Product: NPC111585

Natural Product ID	NPC111585
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Tsugaric Acid A
IUPAC Name	(2R)-2-[(3R,5R,10S,13R,14R,17R)-3-acetyloxy-4,4,10,13,14-pentamethyl-2,3,5,6,7,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl]-6-methylhept-5-enoic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL497273
PubChem CID	15292985
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 86 89 0 0 0 0 0 0 0 0999 V2000 -7.8592 -2.6417 -0.0746 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8405 -1.1715 -0.3581 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8670 -0.3854 0.0738 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7683 -0.9512 0.8527 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4067 -0.7617 0.2125 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1074 0.7330 0.0381 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8135 1.0161 -0.5825 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5895 2.5115 -0.7228 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0920 2.7246 -0.6845 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5608 1.3303 -0.8920 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5449 0.5367 -0.0178 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2570 0.9791 1.3993 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2233 -0.9048 -0.1444 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1960 -1.2434 -0.5132 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1519 -0.1588 -0.1738 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7836 1.1204 -0.3577 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7075 2.2434 -0.0292 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1475 1.9182 -0.2200 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4846 0.4721 -0.2578 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4944 -0.4569 0.3564 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4233 -0.4347 1.8446 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9041 -1.8698 -0.0701 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3383 -1.9681 -0.4738 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2935 -1.1671 0.3446 C 0 0 2 0 0 0 0 0 0 0 0 0 4.8931 0.2925 0.2523 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8001 0.9050 -0.8284 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1918 1.0005 1.5206 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5912 -1.3772 -0.2361 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6565 -1.9013 0.4466 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4543 -2.2120 1.6693 O 0 0 0 0 0 0 0 0 0 0 0 0 8.9926 -2.1151 -0.1595 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5743 0.9460 -2.3229 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5190 1.5097 1.1985 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3031 2.4829 1.1140 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0478 1.1880 2.4560 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.9890 -0.6308 -1.1618 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6702 -3.1515 -0.5996 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8628 -2.8339 1.0251 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9077 -3.1225 -0.4486 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9229 0.6673 -0.1712 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9168 -2.0417 0.9673 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7851 -0.5127 1.8718 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6982 -1.2510 0.9100 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4331 -1.1953 -0.7940 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8863 1.0088 -0.7715 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8736 0.6034 -1.6412 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0935 3.0882 0.0716 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9827 2.8546 -1.7012 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7524 3.3298 -1.5737 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7374 3.2107 0.2215 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1307 1.0416 1.5087 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5307 0.2140 2.1551 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5950 1.9988 1.6203 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9774 -1.3950 -0.7903 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3642 -1.3660 0.8820 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2083 -1.5078 -1.5853 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5421 -2.1543 0.0292 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3778 3.0897 -0.7042 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5535 2.6516 0.9949 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4689 2.4159 -1.1847 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7510 2.4841 0.5518 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5368 0.1769 -1.3519 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6013 -1.1594 2.1268 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3227 -0.8315 2.3568 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0892 0.5337 2.2621 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7163 -2.6084 0.7360 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3085 -2.2004 -0.9492 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6292 -3.0480 -0.3944 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4921 -1.6997 -1.5389 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3990 -1.5168 1.3943 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8605 0.7002 -0.6092 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6737 2.0256 -0.8079 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5186 0.5708 -1.8279 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8490 1.8952 1.3775 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3469 1.3239 2.1175 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8034 0.3196 2.1832 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9285 -2.4633 -1.2117 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6434 -1.2178 -0.0570 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4974 -2.9455 0.3996 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1929 0.1071 -2.6203 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4629 0.7441 -2.7280 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9007 1.8466 -2.9241 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5766 1.3406 3.3082 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8531 0.4147 -1.4390 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1736 -1.3214 -1.9943 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9042 -0.6722 -0.5112 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 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 11 12 1 1 11 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 1 20 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 25 27 1 0 24 28 1 0 28 29 1 0 29 30 2 0 29 31 1 0 10 32 1 6 6 33 1 0 33 34 2 0 33 35 1 0 2 36 1 0 11 7 1 0 20 15 1 0 16 10 1 0 25 19 1 0 1 37 1 0 1 38 1 0 1 39 1 0 3 40 1 0 4 41 1 0 4 42 1 0 5 43 1 0 5 44 1 0 6 45 1 6 7 46 1 6 8 47 1 0 8 48 1 0 9 49 1 0 9 50 1 0 12 51 1 0 12 52 1 0 12 53 1 0 13 54 1 0 13 55 1 0 14 56 1 0 14 57 1 0 17 58 1 0 17 59 1 0 18 60 1 0 18 61 1 0 19 62 1 6 21 63 1 0 21 64 1 0 21 65 1 0 22 66 1 0 22 67 1 0 23 68 1 0 23 69 1 0 24 70 1 1 26 71 1 0 26 72 1 0 26 73 1 0 27 74 1 0 27 75 1 0 27 76 1 0 31 77 1 0 31 78 1 0 31 79 1 0 32 80 1 0 32 81 1 0 32 82 1 0 35 83 1 0 36 84 1 0 36 85 1 0 36 86 1 0 M END

Standard InCHIKey	FIWGZIBLJWZUEA-CAHOJKFZSA-N
Standard InCHI	InChI=1S/C32H50O4/c1-20(2)10-9-11-22(28(34)35)23-14-18-32(8)25-12-13-26-29(4,5)27(36-21(3)33)16-17-30(26,6)24(25)15-19-31(23,32)7/h10,22-23,26-27H,9,11-19H2,1-8H3,(H,34,35)/t22-,23-,26+,27-,30-,31-,32+/m1/s1
SMILES	CC(=CCC[C@H]([C@H]1CC[C@@]2([C@]1(C)CCC1=C2CC[C@@H]2[C@]1(C)CC[C@H](C2(C)C)OC(=O)C)C)C(=O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	498.37	Volume:	552.417 ? Van der Waals volume.
Dense:	0.902	LogP:	4.916 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.38 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.219 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	23.0
TPSA:	63.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.297	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.727	Fsp³:	0.812
MCE-18:	83.069 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.947	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.004 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.606	Promiscuous compounds:	0.248

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.943	MDCK Permeability:	-4.713
Pgp-inhibitor:	0.998	Pgp-substrate:	0.005
PAMPA:	0.629 ? 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%):	0.359	30% Bioavailability (F30%):	0.102
50% Bioavailability (F50%):	0.892

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.995
Plasma Protein Binding (PPB):	96.14%	Volume Distribution (VD):	-0.107
Fu:	3.723% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.973	BCRP inhibitor:	0.01
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.965	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.625	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.366	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.275
HLM stability:	0.016 ? 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):

3.891

Half-life (T1/2):

0.634

ADMET: Toxicity

hERG Blockers:	0.038	hERG Blockers (10um):	0.164
Human Hepatotoxicity (H-HT):	0.653	Drug-induced Liver Injury (DILI):	0.616
AMES Toxicity:	0.187	Rat Oral Acute Toxicity:	0.39
Maximum Recommended Daily Dose:	0.134	Skin Sensitization:	0.969
Carcinogencity:	0.487	Eye Corrosion:	0.388
Eye Irritation:	0.721	Respiratory Toxicity:	0.596
Drug-induced Neurotoxicity:	0.377	Ototoxicity:	0.412
Hematotoxicity:	0.359	Drug-induced Nephrotoxicity:	0.807
Genotoxicity:	0.409	RPMI-8226 Immunitoxicity:	0.042
A549 Cytotoxicity:	0.066	Hek293 Cytotoxicity:	0.046
BCF:	1.675 ? 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:	4.662 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.996 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.561 ? 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
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.phytochem.2005.10.025]
NPO2085	Ganoderma tsugae	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10785428]
NPO2085	Ganoderma tsugae	Species	Ganodermataceae	Eukaryota	n.a.	fruit body	n.a.	PMID[10785428]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	fruit body	n.a.	PMID[11520245]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12045343]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14695801]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1791484]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	spore	n.a.	PMID[18827358]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	fruiting bodies	Nagano, Japan	2008-MAY	PMID[20039640]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20384295]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	fruiting bodies	n.a.	n.a.	PMID[20702092]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	fruiting bodies	n.a.	n.a.	PMID[21924611]
NPO2085	Ganoderma tsugae	Species	Ganodermataceae	Eukaryota	n.a.	fruit body	n.a.	PMID[21939217]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22014750]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	fruit body	n.a.	PMID[22044278]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	fruiting body	n.a.	n.a.	PMID[22047696]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26222905]
NPO2085	Ganoderma tsugae	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9584403]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	fruit body	n.a.	PMID[9635497]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16609	Ganoderma sinense	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2085	Ganoderma tsugae	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16609	Ganoderma sinense	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO16609	Ganoderma sinense	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2085	Ganoderma tsugae	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	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
ED50	2

Activity Type	# Activity
Cell line	1
Non-molecular	1

Molecular-level activity

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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT550	Cell line	T-24	Homo sapiens	ED50	=	3.1	ug ml-1	PMID[10785428]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	6.8	ug ml-1	PMID[10785428]

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

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 NPC111585 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	21275
0.1-0.2	24641
0.2-0.3	3613
0.3-0.4	235
0.4-0.5	67
0.5-0.6	16
0.6-0.7	8
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC148414
1.0	High Similarity	NPC175628
0.7937	Intermediate Similarity	NPC474889
0.6912	Remote Similarity	NPC608955
0.6818	Remote Similarity	NPC233836
0.6818	Remote Similarity	NPC159046
0.6818	Remote Similarity	NPC187376
0.6667	Remote Similarity	NPC201912
0.6667	Remote Similarity	NPC38350
0.6667	Remote Similarity	NPC601139
0.6571	Remote Similarity	NPC471896
0.589	Remote Similarity	NPC484973
0.5811	Remote Similarity	NPC184848
0.5811	Remote Similarity	NPC69548
0.5541	Remote Similarity	NPC482518
0.5385	Remote Similarity	NPC473648
0.5333	Remote Similarity	NPC26888
0.5278	Remote Similarity	NPC55309
0.5278	Remote Similarity	NPC28252
0.5263	Remote Similarity	NPC478308
0.525	Remote Similarity	NPC473514
0.5205	Remote Similarity	NPC473269
0.5205	Remote Similarity	NPC469400
0.5181	Remote Similarity	NPC265655
0.5135	Remote Similarity	NPC76895
0.5135	Remote Similarity	NPC173272
0.5059	Remote Similarity	NPC129340

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC111585 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6234
0.1-0.2	2842
0.2-0.3	70
0.3-0.4	4
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

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