NPASS Compound

Natural Product: NPC216245

Natural Product ID	NPC216245
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Butyl Lucidenate E2
IUPAC Name	butyl (4R)-4-[(3S,5R,10S,12S,13R,14R,17R)-12-acetyloxy-3-hydroxy-4,4,10,13,14-pentamethyl-7,11,15-trioxo-1,2,3,5,6,12,16,17-octahydrocyclopenta[a]phenanthren-17-yl]pentanoate
Synonyms	Butyl Lucidenate E2
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2337650
PubChem CID	71561377
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 89 92 0 0 0 0 0 0 0 0999 V2000 8.4660 2.0992 3.0108 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2664 0.9419 2.0763 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4983 1.3334 0.6282 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2772 0.1193 -0.2181 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9629 -0.3479 -0.0464 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8271 0.3792 -0.3312 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9163 1.5397 -0.7767 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4589 -0.1970 -0.1164 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8627 -0.6532 -1.4143 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4653 -1.2540 -1.2287 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5415 -0.2918 -0.6175 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5023 1.0117 -1.5040 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2332 1.6816 -1.0997 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0876 2.7337 -1.6013 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3779 0.7936 -0.0784 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0513 -0.5334 -0.6978 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3381 -0.4406 -2.1788 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5275 -1.7373 -0.1646 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5050 -2.7401 -1.2160 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1943 -4.0350 -0.9094 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0638 -4.3102 0.2904 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1739 -5.0515 -1.9896 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0284 -1.4867 0.0414 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6687 -2.5574 0.1695 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6045 -0.1480 0.0785 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8187 0.8844 0.0246 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3763 2.2504 0.1294 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6507 3.2511 0.3008 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8324 2.4703 0.0354 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5811 1.2787 0.6044 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0724 -0.0255 0.1478 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.5550 -0.4443 -1.2316 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6519 -1.0594 1.1361 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8132 -0.5788 1.9112 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7515 0.3414 1.1919 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.0405 1.4915 0.5203 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6275 1.6862 -0.8286 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3031 2.8056 1.2854 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6312 -0.3265 0.3373 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2233 0.9942 1.2867 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6933 -2.4494 -0.3358 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5207 1.6917 4.0491 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6086 2.7904 2.9304 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4002 2.6598 2.7591 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2420 0.5459 2.1686 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9902 0.1387 2.3544 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8465 2.1688 0.3555 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5700 1.6650 0.5203 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9530 -0.6930 0.1394 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4696 0.3453 -1.2992 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8123 0.6091 0.3202 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5453 -0.9559 0.6689 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4932 -1.5221 -1.7666 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9011 0.0882 -2.2056 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1719 -1.6331 -2.2230 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8886 0.0473 0.3475 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3641 1.6388 -1.2849 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5134 0.6897 -2.5570 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3585 -0.9467 -2.8432 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5154 0.5748 -2.5301 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3346 -0.9655 -2.3051 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1530 -2.2228 0.7342 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5853 -6.0163 -1.6312 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7835 -4.7192 -2.8511 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8739 -5.1752 -2.3808 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0730 2.6797 -1.0235 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0714 3.3960 0.5913 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3437 1.3247 1.7168 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6794 0.4069 -1.9244 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8081 -1.1168 -1.7220 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4700 -1.0985 -1.1660 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8954 -1.9744 0.6035 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8149 -1.1997 1.8839 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5431 -0.0976 2.8773 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4211 -1.4816 2.2078 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4152 0.7910 1.9805 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9756 0.7496 -1.3262 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5928 2.2648 -0.6820 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0327 2.3370 -1.5005 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6125 2.8263 2.1594 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3241 2.7015 1.7066 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1981 3.6721 0.6177 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4020 -1.2889 0.2667 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5221 1.5297 1.9463 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0643 1.7124 1.1818 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4744 0.0734 1.8131 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7733 -2.5783 -0.0352 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4888 -3.4074 -0.8701 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1449 -2.4443 0.6056 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 16 17 1 6 16 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 20 22 1 0 18 23 1 0 23 24 2 0 23 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 1 0 30 31 1 0 31 32 1 6 31 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 36 38 1 0 35 39 1 0 15 40 1 1 10 41 1 0 16 11 1 0 31 25 1 0 26 15 1 0 36 30 1 0 1 42 1 0 1 43 1 0 1 44 1 0 2 45 1 0 2 46 1 0 3 47 1 0 3 48 1 0 4 49 1 0 4 50 1 0 8 51 1 0 8 52 1 0 9 53 1 0 9 54 1 0 10 55 1 6 11 56 1 1 12 57 1 0 12 58 1 0 17 59 1 0 17 60 1 0 17 61 1 0 18 62 1 1 22 63 1 0 22 64 1 0 22 65 1 0 29 66 1 0 29 67 1 0 30 68 1 1 32 69 1 0 32 70 1 0 32 71 1 0 33 72 1 0 33 73 1 0 34 74 1 0 34 75 1 0 35 76 1 1 37 77 1 0 37 78 1 0 37 79 1 0 38 80 1 0 38 81 1 0 38 82 1 0 39 83 1 0 40 84 1 0 40 85 1 0 40 86 1 0 41 87 1 0 41 88 1 0 41 89 1 0 M END

Standard InCHIKey	GEKHMMSACYDGPN-MMOMKNLBSA-N
Standard InCHI	InChI=1S/C33H48O8/c1-9-10-15-40-25(38)12-11-18(2)20-16-24(37)33(8)26-21(35)17-22-30(4,5)23(36)13-14-31(22,6)27(26)28(39)29(32(20,33)7)41-19(3)34/h18,20,22-23,29,36H,9-17H2,1-8H3/t18-,20-,22+,23+,29-,31+,32+,33+/m1/s1
SMILES	CCCCOC(=O)CC[C@H]([C@H]1CC(=O)[C@@]2([C@]1(C)[C@H](OC(=O)C)C(=O)C1=C2C(=O)C[C@@H]2[C@]1(C)CC[C@@H](C2(C)C)O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	572.33	Volume:	599.601 ? Van der Waals volume.
Dense:	0.955	LogP:	3.089 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.167 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.953 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	25.0
TPSA:	124.04 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.321	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.047	Fsp³:	0.788
MCE-18:	86.644 ? 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:	0.791	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.143 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.292	Promiscuous compounds:	0.552

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.087	MDCK Permeability:	-4.764
Pgp-inhibitor:	0.642	Pgp-substrate:	0.197
PAMPA:	0.982 ? 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):	0.027
20% Bioavailability (F20%):	0.841	30% Bioavailability (F30%):	0.848
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.964
Plasma Protein Binding (PPB):	82.044%	Volume Distribution (VD):	0.042
Fu:	22.844% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.004
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.987
CYP2C19-inhibitor:	0.991	CYP2C19-substrate:	0.416
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.672
CYP3A4-inhibitor:	0.985	CYP3A4-substrate:	0.981
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.994
HLM stability:	0.837 ? 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):

7.813

Half-life (T1/2):

0.43

ADMET: Toxicity

hERG Blockers:	0.006	hERG Blockers (10um):	0.068
Human Hepatotoxicity (H-HT):	0.507	Drug-induced Liver Injury (DILI):	0.33
AMES Toxicity:	0.728	Rat Oral Acute Toxicity:	0.484
Maximum Recommended Daily Dose:	0.654	Skin Sensitization:	0.999
Carcinogencity:	0.974	Eye Corrosion:	0.006
Eye Irritation:	0.433	Respiratory Toxicity:	0.279
Drug-induced Neurotoxicity:	0.039	Ototoxicity:	0.248
Hematotoxicity:	0.557	Drug-induced Nephrotoxicity:	0.987
Genotoxicity:	0.869	RPMI-8226 Immunitoxicity:	0.246
A549 Cytotoxicity:	0.024	Hek293 Cytotoxicity:	0.175
BCF:	0.624 ? 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:	3.618 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.493 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.941 ? 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]
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]
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]
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]
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]
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
IC50	1

Activity Type	# Activity
Cell line	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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	6400.0	nM	PMID[23357630]

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 NPC216245 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	16520
0.1-0.2	27913
0.2-0.3	5254
0.3-0.4	136
0.4-0.5	16
0.5-0.6	9
0.6-0.7	6
0.7-0.8	0
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
0.8281	Intermediate Similarity	NPC70967
0.7971	Intermediate Similarity	NPC129689
0.7857	Intermediate Similarity	NPC470251
0.7761	Intermediate Similarity	NPC275439
0.6857	Remote Similarity	NPC33973
0.6761	Remote Similarity	NPC135854
0.662	Remote Similarity	NPC77947
0.6429	Remote Similarity	NPC216904
0.64	Remote Similarity	NPC2436
0.6053	Remote Similarity	NPC307954
0.5694	Remote Similarity	NPC88198
0.5513	Remote Similarity	NPC286174
0.5455	Remote Similarity	NPC600112
0.5366	Remote Similarity	NPC472929
0.5316	Remote Similarity	NPC600026
0.5263	Remote Similarity	NPC124211
0.5195	Remote Similarity	NPC112753
0.519	Remote Similarity	NPC7124
0.506	Remote Similarity	NPC115303

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC216245 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6215
0.1-0.2	2755
0.2-0.3	179
0.3-0.4	1
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