NPASS Compound

Natural Product: NPC456

Natural Product ID	NPC456
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	11Beta-Hydroxy-3,7-Dioxo-5Alpha-Lanosta-8,24(E)-Dien-26-Oic Acid
IUPAC Name	(E,6R)-6-[(5R,10S,11S,13R,14R,17R)-11-hydroxy-4,4,10,13,14-pentamethyl-3,7-dioxo-2,5,6,11,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methylhept-2-enoic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2203594
PubChem CID	46910043
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 79 82 0 0 0 0 0 0 0 0999 V2000 3.0791 -0.3473 -2.0800 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0237 0.6482 -0.9592 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0451 0.2057 0.0941 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0232 1.2355 1.2380 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6179 1.2377 1.7718 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0621 0.0914 1.0581 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6167 0.1918 -0.2924 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2169 1.4876 -0.9629 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1599 -0.9831 -1.1025 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3221 -1.1952 -1.0737 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8711 -1.0876 -2.3733 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0635 -0.3117 -0.1714 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5022 0.3262 0.8639 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2397 1.1853 1.7462 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7567 1.5925 2.8108 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6087 1.5805 1.3544 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2095 0.2971 0.7650 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5347 -0.1484 -0.4812 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5886 0.8757 -1.5969 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1634 -1.4335 -0.9306 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1321 -2.0250 0.0905 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1726 -1.0244 0.4272 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3359 -1.3545 0.4437 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6994 0.3507 0.7288 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3005 1.2894 -0.2456 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1693 0.7599 2.1205 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1881 -1.2150 1.7295 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4252 0.7911 -0.4074 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9793 -0.4922 0.1169 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3552 -0.2093 0.6257 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4359 -0.7960 0.1538 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7734 -0.4938 0.6777 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7643 -1.0760 0.1973 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8735 0.4406 1.6992 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2722 -1.7965 -0.9491 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7332 -1.3647 -1.8175 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1426 -0.4290 -2.4883 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5069 -0.0328 -2.9821 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6810 1.6060 -1.3967 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3903 -0.7245 0.5433 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2168 2.2556 0.8247 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7589 0.9595 2.0179 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1022 2.2057 1.5897 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6269 0.9986 2.8549 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7895 1.8270 -0.6422 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1907 1.4067 -2.0691 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9003 2.3291 -0.7280 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6964 -1.8923 -0.7735 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4407 -0.8001 -2.1559 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5013 -2.2682 -0.7704 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3148 -1.6175 -2.9905 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2392 1.8656 2.2164 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6021 2.4108 0.6559 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9584 -0.4870 1.5463 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1910 0.4532 -2.4334 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5950 1.1010 -2.0388 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9863 1.8566 -1.2646 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4818 -2.2448 -1.1769 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7936 -1.2741 -1.8523 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5955 -2.3997 0.9810 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6063 -2.8801 -0.3960 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9863 2.3558 -0.0456 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2284 1.0101 -1.2988 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4103 1.3127 -0.0225 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5074 0.3921 2.9113 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2101 0.3619 2.2341 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2764 1.8624 2.1050 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8868 -1.8926 1.2470 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7970 -1.7378 1.8709 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6104 -0.9904 2.7430 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4928 1.5478 0.3872 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0791 1.1280 -1.2369 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4127 -0.8916 0.9869 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1054 -1.2681 -0.6792 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4779 0.5221 1.4319 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7755 0.8815 1.8267 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7994 -1.2696 -1.8233 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2641 -2.1230 -1.3009 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6620 -2.6592 -0.6495 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 10 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 1 0 17 18 1 0 18 19 1 6 18 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 1 0 24 26 1 0 6 27 1 1 2 28 1 0 28 29 1 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 32 34 1 0 31 35 1 0 7 3 1 0 18 12 1 0 13 6 1 0 24 17 1 0 1 36 1 0 1 37 1 0 1 38 1 0 2 39 1 6 3 40 1 1 4 41 1 0 4 42 1 0 5 43 1 0 5 44 1 0 8 45 1 0 8 46 1 0 8 47 1 0 9 48 1 0 9 49 1 0 10 50 1 1 11 51 1 0 16 52 1 0 16 53 1 0 17 54 1 1 19 55 1 0 19 56 1 0 19 57 1 0 20 58 1 0 20 59 1 0 21 60 1 0 21 61 1 0 25 62 1 0 25 63 1 0 25 64 1 0 26 65 1 0 26 66 1 0 26 67 1 0 27 68 1 0 27 69 1 0 27 70 1 0 28 71 1 0 28 72 1 0 29 73 1 0 29 74 1 0 30 75 1 0 34 76 1 0 35 77 1 0 35 78 1 0 35 79 1 0 M END

Standard InCHIKey	SAZFHNNKAYSDKP-LOHDOYQRSA-N
Standard InCHI	InChI=1S/C30H44O5/c1-17(9-8-10-18(2)26(34)35)19-11-14-29(6)25-20(31)15-22-27(3,4)23(33)12-13-28(22,5)24(25)21(32)16-30(19,29)7/h10,17,19,21-22,32H,8-9,11-16H2,1-7H3,(H,34,35)/b18-10+/t17-,19-,21+,22+,28+,29+,30-/m1/s1
SMILES	C[C@@H]([C@H]1CC[C@@]2([C@]1(C)C[C@H](O)C1=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:	484.32	Volume:	523.979 ? Van der Waals volume.
Dense:	0.924	LogP:	3.639 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.125 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.062 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	91.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.474	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.912	Fsp³:	0.767
MCE-18:	84.679 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.841	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.007 ? 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:	0.362	Promiscuous compounds:	0.331

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.384	MDCK Permeability:	-4.986
Pgp-inhibitor:	0.724	Pgp-substrate:	0.003
PAMPA:	0.983 ? 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):	0.005
20% Bioavailability (F20%):	0.509	30% Bioavailability (F30%):	0.517
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.995
Plasma Protein Binding (PPB):	80.418%	Volume Distribution (VD):	-0.445
Fu:	18.539% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.022
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.94	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.003
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.004
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.952
HLM stability:	0.319 ? 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):

4.619

Half-life (T1/2):

0.892

ADMET: Toxicity

hERG Blockers:	0.006	hERG Blockers (10um):	0.014
Human Hepatotoxicity (H-HT):	0.841	Drug-induced Liver Injury (DILI):	0.747
AMES Toxicity:	0.166	Rat Oral Acute Toxicity:	0.137
Maximum Recommended Daily Dose:	0.582	Skin Sensitization:	0.993
Carcinogencity:	0.575	Eye Corrosion:	0.005
Eye Irritation:	0.654	Respiratory Toxicity:	0.76
Drug-induced Neurotoxicity:	0.027	Ototoxicity:	0.774
Hematotoxicity:	0.782	Drug-induced Nephrotoxicity:	0.991
Genotoxicity:	0.948	RPMI-8226 Immunitoxicity:	0.072
A549 Cytotoxicity:	0.023	Hek293 Cytotoxicity:	0.08
BCF:	0.62 ? 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:	3.679 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.362 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.418 ? 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]
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
IC50	2
Ratio	1

Activity Type	# Activity
Individual protein	2
Cell line	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1648	Individual protein	Oligo-1,6-glucosidase	Saccharomyces cerevisiae S288c	IC50	=	119060.0	nM	PubChem BioAssay data set
NPT668	Individual protein	P-glycoprotein 1	Homo sapiens	Ratio	=	3.0	n.a.	PMID[8277313]

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	=	11000.0	nM	PMID[1965654]

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 NPC456 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	20137
0.1-0.2	25690
0.2-0.3	3571
0.3-0.4	356
0.4-0.5	72
0.5-0.6	24
0.6-0.7	2
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	NPC472941
1.0	High Similarity	NPC202814
0.7273	Intermediate Similarity	NPC162703
0.7164	Intermediate Similarity	NPC8571
0.6528	Remote Similarity	NPC489798
0.6053	Remote Similarity	NPC472924
0.5915	Remote Similarity	NPC142253
0.5915	Remote Similarity	NPC3511
0.5811	Remote Similarity	NPC601194
0.5753	Remote Similarity	NPC87552
0.5584	Remote Similarity	NPC482514
0.5526	Remote Similarity	NPC483394
0.5513	Remote Similarity	NPC472925
0.5513	Remote Similarity	NPC604630
0.5479	Remote Similarity	NPC41539
0.5467	Remote Similarity	NPC472239
0.5385	Remote Similarity	NPC489789
0.5342	Remote Similarity	NPC472931
0.5278	Remote Similarity	NPC16287
0.527	Remote Similarity	NPC472940
0.5205	Remote Similarity	NPC99909
0.519	Remote Similarity	NPC285702
0.519	Remote Similarity	NPC166745
0.519	Remote Similarity	NPC235464
0.5125	Remote Similarity	NPC478297
0.5119	Remote Similarity	NPC472926
0.5119	Remote Similarity	NPC198442
0.5068	Remote Similarity	NPC90965
0.5065	Remote Similarity	NPC479655
0.5065	Remote Similarity	NPC489792

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC456 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6032
0.1-0.2	2962
0.2-0.3	156
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