NPASS Compound

Natural Product: NPC8571

Natural Product ID	NPC8571
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ganoderic Acid Dm
IUPAC Name	(Z,6R)-2-methyl-6-[(5R,10S,13R,14R,17R)-4,4,10,13,14-pentamethyl-3,7-dioxo-2,5,6,11,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthren-17-yl]hept-2-enoic acid
Synonyms	Ganoderic acid DM
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1099224
PubChem CID	46888220
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 78 81 0 0 0 0 0 0 0 0999 V2000 4.3828 -0.5515 1.2874 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3253 -0.1027 0.3178 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0133 -0.2708 0.9912 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8147 0.5022 2.2598 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2911 0.5831 2.4551 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2086 -0.3499 1.3905 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7753 0.0331 0.2591 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4939 1.4878 0.0041 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4656 -0.7713 -0.9307 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8950 -0.4563 -1.4506 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8689 -0.0988 -0.3850 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5526 -0.0539 0.8907 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6171 0.3002 1.8155 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3505 1.0284 2.8249 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0175 -0.1950 1.5732 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2048 -0.5183 0.0951 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.2578 0.2446 -0.7688 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4507 1.7465 -0.6670 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4558 -0.0942 -2.2342 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8557 0.2605 -2.6592 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8653 -0.2246 -1.7025 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9988 -0.4588 -2.1475 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6469 -0.4527 -0.2790 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2661 -1.8222 0.0450 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4350 0.5402 0.5406 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0265 -1.7505 1.8600 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6152 1.1971 -0.2656 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8880 1.2359 -1.0640 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1337 0.9707 -0.3575 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9766 0.0169 -0.5438 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8044 -1.0012 -1.5430 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7536 -1.8800 -1.5955 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7754 -1.1569 -2.4342 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2018 -0.0218 0.3385 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0244 -1.3717 0.9092 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0083 0.2718 1.6569 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9141 -0.9789 2.2247 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3421 -0.8770 -0.5011 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9546 -1.3610 1.2910 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2642 -0.0265 3.1333 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2622 1.4960 2.1719 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0199 0.2224 3.4669 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0026 1.6246 2.3378 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5262 1.8095 0.3792 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1752 2.1733 0.5838 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4478 1.7387 -1.0759 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5620 -1.8614 -0.8088 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2064 -0.5073 -1.7422 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8227 0.3485 -2.2112 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2766 -1.3609 -2.0090 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7010 0.5819 1.9424 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1409 -1.0820 2.2252 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8953 -1.5940 -0.0025 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2404 2.1538 0.3206 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6699 2.1883 -1.3547 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4129 2.0236 -1.0935 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7553 0.5225 -2.8316 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2366 -1.1604 -2.4622 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9959 1.3276 -2.9127 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0333 -0.2899 -3.6289 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1627 -2.0159 -0.5531 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5305 -2.6383 -0.1379 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5839 -1.8415 1.1262 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9713 1.5153 0.6531 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6827 0.1554 1.5570 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4254 0.7150 0.0402 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6301 -1.7912 2.7787 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0302 -2.0941 2.2509 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2617 -2.4803 1.1075 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7308 2.0083 0.5048 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8147 1.4814 -0.9990 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0323 2.3363 -1.4425 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8066 0.6770 -2.0092 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4017 1.7001 0.4451 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9939 -1.5919 -3.3307 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9382 -0.2262 1.3868 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8935 -0.8247 0.0101 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6691 0.9880 0.3075 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 1 0 7 8 1 6 7 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 6 17 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 1 0 23 25 1 0 6 26 1 1 2 27 1 0 27 28 1 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 31 33 1 0 30 34 1 0 7 3 1 0 17 11 1 0 12 6 1 0 23 16 1 0 1 35 1 0 1 36 1 0 1 37 1 0 2 38 1 6 3 39 1 1 4 40 1 0 4 41 1 0 5 42 1 0 5 43 1 0 8 44 1 0 8 45 1 0 8 46 1 0 9 47 1 0 9 48 1 0 10 49 1 0 10 50 1 0 15 51 1 0 15 52 1 0 16 53 1 1 18 54 1 0 18 55 1 0 18 56 1 0 19 57 1 0 19 58 1 0 20 59 1 0 20 60 1 0 24 61 1 0 24 62 1 0 24 63 1 0 25 64 1 0 25 65 1 0 25 66 1 0 26 67 1 0 26 68 1 0 26 69 1 0 27 70 1 0 27 71 1 0 28 72 1 0 28 73 1 0 29 74 1 0 33 75 1 0 34 76 1 0 34 77 1 0 34 78 1 0 M END

Standard InCHIKey	ZTKZZRIVAYGFSF-YQDYMHCHSA-N
Standard InCHI	InChI=1S/C30H44O4/c1-18(9-8-10-19(2)26(33)34)20-11-16-30(7)25-21(12-15-29(20,30)6)28(5)14-13-24(32)27(3,4)23(28)17-22(25)31/h10,18,20,23H,8-9,11-17H2,1-7H3,(H,33,34)/b19-10-/t18-,20-,23+,28-,29-,30+/m1/s1
SMILES	C[C@@H]([C@H]1CC[C@@]2([C@]1(C)CCC1=C2C(=O)C[C@@H]2[C@]1(C)CCC(=O)C2(C)C)C)CC/C=C(C(=O)O)/C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	468.32	Volume:	515.189 ? Van der Waals volume.
Dense:	0.909	LogP:	4.296 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.406 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.79 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	71.44 ? 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:	0.444	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.699	Fsp³:	0.767
MCE-18:	82.189 ? 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:	0.919	Fluc inhibitor:	0.004 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.024 ? 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:	0.564	Promiscuous compounds:	0.245

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.998	MDCK Permeability:	-4.751
Pgp-inhibitor:	0.123	Pgp-substrate:	0.0
PAMPA:	0.959 ? 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%):	0.086	30% Bioavailability (F30%):	0.234
50% Bioavailability (F50%):	0.947

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.986
Plasma Protein Binding (PPB):	89.856%	Volume Distribution (VD):	-0.166
Fu:	11.513% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.011
BSEP inhibitor:	0.889

ADMET: Metabolism

CYP1A2-inhibitor:	0.388	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.021
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.964
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.841
HLM stability:	0.925 ? 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):

4.17

Half-life (T1/2):

0.644

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.023
Human Hepatotoxicity (H-HT):	0.791	Drug-induced Liver Injury (DILI):	0.786
AMES Toxicity:	0.155	Rat Oral Acute Toxicity:	0.217
Maximum Recommended Daily Dose:	0.405	Skin Sensitization:	0.987
Carcinogencity:	0.639	Eye Corrosion:	0.11
Eye Irritation:	0.772	Respiratory Toxicity:	0.715
Drug-induced Neurotoxicity:	0.075	Ototoxicity:	0.692
Hematotoxicity:	0.854	Drug-induced Nephrotoxicity:	0.974
Genotoxicity:	0.856	RPMI-8226 Immunitoxicity:	0.047
A549 Cytotoxicity:	0.019	Hek293 Cytotoxicity:	0.072
BCF:	0.711 ? 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:	3.929 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.497 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.6 ? 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]
NPO33020	ganoderma leucocontextum	Species	Ganodermataceae	Eukaryota	fruiting bodies	Tibetan	n.a.	PMID[26287401]
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]
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]
NPO25269	Ganoderma lucidum	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[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
Activity	1
IC50	11
Inhibition	1
CC50	1

Activity Type	# Activity
Individual protein	3
Cell line	6
Others	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT153	Individual protein	Androgen Receptor	Homo sapiens	Activity	=	50.0	%	PMID[19289282]
NPT1088	Individual protein	3-hydroxy-3-methylglutaryl-coenzyme A reductase	Sus scrofa	IC50	=	9500.0	nM	PMID[26287401]
NPT1088	Individual protein	3-hydroxy-3-methylglutaryl-coenzyme A reductase	Sus scrofa	IC50	=	56100.0	nM	PMID[26287401]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	101000.0	nM	PMID[23092389]
NPT111	Cell line	K562	Homo sapiens	IC50	=	18800.0	nM	PMID[26287401]
NPT111	Cell line	K562	Homo sapiens	IC50	=	55400.0	nM	PMID[26287401]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	81600.0	nM	PMID[26287401]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	148600.0	nM	PMID[26287401]
NPT113	Cell line	RAW264.7	Mus musculus	CC50	=	65000.0	nM	PMID[31035236]
NPT2	Others	Unspecified	n.a.	IC50	=	10600.0	nM	PMID[23092389]
NPT2	Others	Unspecified	n.a.	Inhibition	=	40.0	%	PMID[19289282]
NPT2	Others	Unspecified	n.a.	IC50	>	50000.0	nM	PMID[26287401]

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 NPC8571 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	26242
0.1-0.2	20918
0.2-0.3	2251
0.3-0.4	309
0.4-0.5	91
0.5-0.6	26
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
0.8197	Intermediate Similarity	NPC162703
0.7742	Intermediate Similarity	NPC142253
0.7742	Intermediate Similarity	NPC3511
0.7273	Intermediate Similarity	NPC601194
0.7258	Intermediate Similarity	NPC90965
0.7188	Intermediate Similarity	NPC41539
0.7164	Intermediate Similarity	NPC456
0.7164	Intermediate Similarity	NPC472941
0.7164	Intermediate Similarity	NPC202814
0.7143	Intermediate Similarity	NPC605549
0.7101	Intermediate Similarity	NPC478297
0.7059	Intermediate Similarity	NPC489798
0.6957	Remote Similarity	NPC489789
0.6923	Remote Similarity	NPC472940
0.6615	Remote Similarity	NPC99909
0.6471	Remote Similarity	NPC87552
0.6143	Remote Similarity	NPC318332
0.6143	Remote Similarity	NPC472239
0.5915	Remote Similarity	NPC489792
0.5733	Remote Similarity	NPC489802
0.5733	Remote Similarity	NPC604630
0.5616	Remote Similarity	NPC479661
0.5571	Remote Similarity	NPC472931
0.5507	Remote Similarity	NPC16287
0.5467	Remote Similarity	NPC69982
0.5455	Remote Similarity	NPC472924
0.5429	Remote Similarity	NPC275740
0.5429	Remote Similarity	NPC86319
0.5417	Remote Similarity	NPC69454
0.5325	Remote Similarity	NPC489807
0.5325	Remote Similarity	NPC489808
0.5325	Remote Similarity	NPC478298
0.5325	Remote Similarity	NPC489800
0.5309	Remote Similarity	NPC489806
0.5309	Remote Similarity	NPC198442
0.5195	Remote Similarity	NPC285702
0.5195	Remote Similarity	NPC166745
0.5195	Remote Similarity	NPC235464
0.5132	Remote Similarity	NPC483394
0.5125	Remote Similarity	NPC478311
0.5065	Remote Similarity	NPC482515
0.5065	Remote Similarity	NPC482517
0.5062	Remote Similarity	NPC478309
0.5062	Remote Similarity	NPC489799

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC8571 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6673
0.1-0.2	2356
0.2-0.3	121
0.3-0.4	0
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