NPASS Compound

Natural Product: NPC476888

Natural Product ID	NPC476888
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(4R,4aS,6aR,6aS,6bR,8aR,12aR,14bR)-2,2,6a,6b,9,9,12a-heptamethyl-4-(3-methylbut-2-enoyloxy)-10-oxo-3,4,5,6,6a,7,8,8a,11,12,13,14b-dodecahydro-1H-picene-4a-carboxylic acid
IUPAC Name	(4R,4aS,6aR,6aS,6bR,8aR,12aR,14bR)-2,2,6a,6b,9,9,12a-heptamethyl-4-(3-methylbut-2-enoyloxy)-10-oxo-3,4,5,6,6a,7,8,8a,11,12,13,14b-dodecahydro-1H-picene-4a-carboxylic acid
Synonyms	Lantadene B
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	45269863
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 92 96 0 0 0 0 0 0 0 0999 V2000 8.8164 1.7400 -1.3275 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7667 1.4638 -0.3244 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7470 0.6992 -0.6466 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6705 0.3811 0.2906 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6833 0.8221 1.4273 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6523 -0.4086 -0.1070 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5251 -0.8340 0.6205 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5527 -2.3076 0.9027 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9724 -3.1353 -0.2106 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6810 -2.5819 -0.7415 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2492 -1.4323 0.0848 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2345 -0.3018 0.0830 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7383 0.8592 0.9170 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4206 0.6964 1.5647 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6462 -0.0539 0.8672 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0749 -0.8482 -0.2581 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6567 -1.0283 -1.4203 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9787 -0.4393 -1.7465 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6761 -0.0970 -0.4377 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7953 0.8015 0.3431 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4602 1.5614 1.4594 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7515 2.1440 0.9248 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6447 0.9839 0.5900 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0981 0.3042 -0.6181 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8961 -0.9847 -0.8543 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2464 -0.9792 -0.2376 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8289 0.3860 -0.2092 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8796 0.6528 -0.7469 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0537 1.4206 0.5182 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6029 1.4245 1.9532 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2712 2.8032 -0.0289 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3491 1.1354 -1.8715 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1399 1.8815 -0.5307 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2082 -1.1103 1.8350 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3565 0.1759 -1.3157 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1375 1.4198 -1.5320 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6777 -0.5374 -2.4258 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7261 -4.5314 0.3087 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0137 -3.2586 -1.2998 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8627 2.0471 1.0458 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7385 0.9811 -2.1582 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8208 1.5497 -0.8684 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7631 2.7762 -1.7205 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7317 0.2984 -1.6701 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6700 -0.3547 1.6214 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9333 -2.4854 1.8012 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5658 -2.6590 1.2011 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8969 -3.3881 -0.5610 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6509 -2.4571 -1.8322 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1739 -1.8243 1.1431 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7866 1.8213 0.3216 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5013 1.0412 1.7228 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0955 1.7433 1.8611 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6092 0.2302 2.5812 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1748 -1.6241 -2.1856 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8187 0.4130 -2.4072 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5615 -1.2586 -2.2332 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6997 -1.0878 0.1136 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6260 0.9635 2.3682 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8245 2.4723 1.6904 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2586 2.7788 1.6874 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5117 2.8007 0.0884 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5410 0.2566 1.4479 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3298 -1.8646 -0.4578 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0138 -1.1887 -1.9427 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1997 -1.3330 0.8329 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9332 -1.6256 -0.8174 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2785 2.3908 2.3942 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1296 0.6299 2.5531 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6987 1.4101 1.9605 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4403 3.4892 0.1753 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5579 2.8131 -1.1104 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1668 3.2617 0.4862 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7865 0.7356 -2.7371 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2292 2.2037 -1.7186 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4302 0.9851 -2.1680 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8900 2.4963 -1.0674 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5947 2.5826 0.1384 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5169 1.4129 -1.2824 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9792 -2.1461 1.4992 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6666 -1.0219 2.8197 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2601 -0.9713 2.0675 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3716 -0.1230 -3.0664 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1198 -5.1015 -0.4545 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1223 -4.5393 1.2323 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6756 -5.1223 0.4074 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8588 -2.5562 -1.1491 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5767 -3.1293 -2.3171 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4829 -4.2766 -1.3274 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9337 1.2688 1.8160 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7882 2.6827 1.1341 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0254 2.7162 1.2415 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 2 0 4 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 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 1 0 29 31 1 0 24 32 1 6 20 33 1 6 15 34 1 1 12 35 1 6 35 36 2 0 35 37 1 0 9 38 1 0 9 39 1 0 2 40 1 0 12 7 1 0 16 11 1 0 20 15 1 0 24 19 1 0 29 23 1 0 1 41 1 0 1 42 1 0 1 43 1 0 3 44 1 0 7 45 1 1 8 46 1 0 8 47 1 0 10 48 1 0 10 49 1 0 11 50 1 1 13 51 1 0 13 52 1 0 14 53 1 0 14 54 1 0 17 55 1 0 18 56 1 0 18 57 1 0 19 58 1 1 21 59 1 0 21 60 1 0 22 61 1 0 22 62 1 0 23 63 1 1 25 64 1 0 25 65 1 0 26 66 1 0 26 67 1 0 30 68 1 0 30 69 1 0 30 70 1 0 31 71 1 0 31 72 1 0 31 73 1 0 32 74 1 0 32 75 1 0 32 76 1 0 33 77 1 0 33 78 1 0 33 79 1 0 34 80 1 0 34 81 1 0 34 82 1 0 37 83 1 0 38 84 1 0 38 85 1 0 38 86 1 0 39 87 1 0 39 88 1 0 39 89 1 0 40 90 1 0 40 91 1 0 40 92 1 0 M END

Standard InCHIKey	VYPAPFHUHDWCBI-CNSFRLJCSA-N
Standard InCHI	InChI=1S/C35H52O5/c1-21(2)18-28(37)40-27-20-30(3,4)19-23-22-10-11-25-32(7)14-13-26(36)31(5,6)24(32)12-15-34(25,9)33(22,8)16-17-35(23,27)29(38)39/h10,18,23-25,27H,11-17,19-20H2,1-9H3,(H,38,39)/t23-,24+,25-,27-,32+,33-,34-,35+/m1/s1
SMILES	CC(=CC(=O)O[C@@H]1CC(C[C@H]2[C@]1(CC[C@@]3(C2=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CCC(=O)C5(C)C)C)C)C)C(=O)O)(C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	552.38	Volume:	601.902 ? Van der Waals volume.
Dense:	0.918	LogP:	4.982 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.82 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.133 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	30.0
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:	0.218	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.992	Fsp³:	0.8
MCE-18:	109.333 ? 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:	0.865	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.008 ? 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:	0.412	Promiscuous compounds:	0.084

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.464	MDCK Permeability:	-5.051
Pgp-inhibitor:	0.151	Pgp-substrate:	0.0
PAMPA:	0.993 ? 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):	0.001
20% Bioavailability (F20%):	0.034	30% Bioavailability (F30%):	0.02
50% Bioavailability (F50%):	0.983

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.124	MRP1:	0.98
Plasma Protein Binding (PPB):	97.212%	Volume Distribution (VD):	0.092
Fu:	2.975% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.039
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.989	CYP1A2-substrate:	0.02
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.212
CYP2C9-inhibitor:	0.005	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.011
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.947
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.039
HLM stability:	0.581 ? 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):

3.032

Half-life (T1/2):

0.757

ADMET: Toxicity

hERG Blockers:	0.012	hERG Blockers (10um):	0.02
Human Hepatotoxicity (H-HT):	0.633	Drug-induced Liver Injury (DILI):	0.884
AMES Toxicity:	0.299	Rat Oral Acute Toxicity:	0.567
Maximum Recommended Daily Dose:	0.607	Skin Sensitization:	0.952
Carcinogencity:	0.788	Eye Corrosion:	0.005
Eye Irritation:	0.097	Respiratory Toxicity:	0.785
Drug-induced Neurotoxicity:	0.115	Ototoxicity:	0.501
Hematotoxicity:	0.869	Drug-induced Nephrotoxicity:	0.988
Genotoxicity:	0.981	RPMI-8226 Immunitoxicity:	0.064
A549 Cytotoxicity:	0.137	Hek293 Cytotoxicity:	0.167
BCF:	0.991 ? 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:	3.955 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.565 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.874 ? 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
NPO33642	Combretum sundaicum	Species	Combretaceae	Eukaryota	leaves, flowers	Bac Son, Lang Son Province, Vietnam	1997-JUL	PMID[19572612]
NPO33642	Combretum sundaicum	Species	Combretaceae	Eukaryota	leaves	Bac Son, Lang Son Province, Vietnam	1997-JUL	PMID[19572612]
NPO33642	Combretum sundaicum	Species	Combretaceae	Eukaryota	flowers	Bac Son, Lang Son Province, Vietnam	1997-JUL	PMID[19572612]

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
Ki	1
IC50	9

Activity Type	# Activity
Individual protein	1
Cell line	9

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2796	Individual protein	Apoptosis regulator Bcl-X	Homo sapiens	Ki	>	100000	nM	PMID[19572612]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	11400	nM	PMID[19572612]
NPT137	Cell line	L1210	Mus musculus	IC50	=	16100	nM	PMID[19572612]
NPT91	Cell line	KB	Homo sapiens	IC50	=	25300	nM	PMID[19572612]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	44000	nM	PMID[19572612]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	13200	nM	DOI[10.1007/s00044-012-0354-x]
NPT116	Cell line	HL-60	Homo sapiens	IC50	=	19100	nM	DOI[10.1007/s00044-012-0354-x]
NPT924	Cell line	HSC-2	Homo sapiens	IC50	=	43000	nM	DOI[10.1007/s00044-012-0354-x]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	81400	nM	DOI[10.1007/s00044-012-0354-x]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	>	50000	nM	DOI[10.1007/s00044-012-0354-x]

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 NPC476888 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	23087
0.1-0.2	23084
0.2-0.3	2957
0.3-0.4	581
0.4-0.5	124
0.5-0.6	17
0.6-0.7	4
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC93744
0.8571	High Similarity	NPC600880
0.8493	Intermediate Similarity	NPC476890
0.7089	Intermediate Similarity	NPC476889
0.6625	Remote Similarity	NPC40918
0.6506	Remote Similarity	NPC475570
0.622	Remote Similarity	NPC603645
0.6	Remote Similarity	NPC267691
0.5875	Remote Similarity	NPC488521
0.5862	Remote Similarity	NPC607691
0.5789	Remote Similarity	NPC274050
0.5789	Remote Similarity	NPC162632
0.5769	Remote Similarity	NPC158141
0.5595	Remote Similarity	NPC23241
0.557	Remote Similarity	NPC38754
0.5455	Remote Similarity	NPC473576
0.5443	Remote Similarity	NPC263272
0.5393	Remote Similarity	NPC473483
0.5309	Remote Similarity	NPC120840
0.5122	Remote Similarity	NPC173089
0.5122	Remote Similarity	NPC200752
0.5119	Remote Similarity	NPC296164
0.5109	Remote Similarity	NPC110861
0.5062	Remote Similarity	NPC474845
0.506	Remote Similarity	NPC193750

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476888 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6386
0.1-0.2	2718
0.2-0.3	38
0.3-0.4	7
0.4-0.5	1
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