NPASS Compound

Natural Product: NPC12557

Natural Product ID	NPC12557
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	IZUDZNKPPXKFJY-MCCGTYTDSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	9987097
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0002119] Quassinoids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 2D 92 97 0 0 0 0 0 0 0 0999 V2000 -8.6834 1.5924 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2926 1.0305 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1106 1.9540 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7198 1.3921 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5110 -0.0933 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5378 2.3156 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1470 1.7537 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2760 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 -1.2135 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3273 -0.2783 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1683 -0.2563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5090 0.2098 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9356 0.6734 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3622 1.1369 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2475 2.1406 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1328 3.1443 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7062 2.6807 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4086 3.6844 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8351 3.2209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9499 4.2246 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6741 2.6041 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7888 1.6004 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4769 0.1332 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0503 -0.3303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8683 -1.2538 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6857 -1.3522 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0764 -1.9141 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2816 -3.1862 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9858 -4.5106 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4849 -4.5630 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2797 -3.2909 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.4617 -2.3674 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.6438 -1.4439 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5755 -1.9665 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8756 -5.1249 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1945 -5.9960 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0995 -4.1097 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9859 4.0713 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7663 -1.2523 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6287 -3.0903 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2458 -1.6317 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2720 -3.1314 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6161 -1.0216 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8297 -1.9033 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0838 -0.4549 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.0741 2.1544 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2453 0.2017 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1215 2.9832 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3193 3.4394 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0910 0.5880 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3180 -0.0226 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1147 1.2436 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3907 -1.0037 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1465 -2.9097 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5447 -2.7444 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9226 -1.2320 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8585 1.2414 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4413 0.0950 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6228 2.6141 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5593 3.6078 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5952 4.5447 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0562 4.3263 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8369 4.1750 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2154 2.0639 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9712 0.2640 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5878 -1.7307 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2566 -2.7027 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5648 -0.4959 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0528 -2.3259 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6263 -5.1446 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1730 -6.0302 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3944 -4.2946 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 11.3852 -3.5494 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5383 -1.1854 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 11.4350 0.0415 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0844 -6.6103 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0125 -6.9195 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1257 -5.6095 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2978 5.5385 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4531 3.7595 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6378 4.7290 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3689 -2.6259 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1055 -4.3983 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0432 -2.7849 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5568 -0.5913 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9480 -3.1168 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8751 -1.9403 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5692 -0.6636 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6349 -0.0666 0.0000 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 1 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 1 1 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 18 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 27 28 1 0 26 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 34 37 1 0 33 38 1 0 32 39 1 0 31 40 1 0 24 41 1 0 14 42 1 0 13 43 1 0 12 44 1 1 44 45 2 0 44 46 1 0 46 47 1 0 2 48 1 0 22 7 1 0 37 30 1 0 12 8 1 0 27 16 1 0 20 9 1 0 15 9 1 0 1 49 1 0 1 50 1 0 1 51 1 0 3 52 1 0 7 53 1 6 8 54 1 1 10 55 1 0 10 56 1 0 13 57 1 1 14 58 1 1 15 59 1 6 17 60 1 0 17 61 1 0 17 62 1 0 18 63 1 6 19 64 1 0 19 65 1 0 20 66 1 1 25 67 1 0 26 68 1 1 27 69 1 6 28 70 1 0 30 71 1 1 31 72 1 6 32 73 1 1 33 74 1 6 34 75 1 1 35 76 1 0 35 77 1 0 36 78 1 0 38 79 1 0 39 80 1 0 40 81 1 0 41 82 1 0 41 83 1 0 41 84 1 0 42 85 1 0 43 86 1 0 47 87 1 0 47 88 1 0 47 89 1 0 48 90 1 0 48 91 1 0 48 92 1 0 M END

Standard InCHIKey	IZUDZNKPPXKFJY-MCCGTYTDSA-N
Standard InCHI	InChI=1S/C32H44O16/c1-11(2)6-17(34)48-22-24-31-10-44-32(24,29(42)43-5)26(40)21(38)23(31)30(4)13(8-16(31)47-27(22)41)12(3)7-14(25(30)39)45-28-20(37)19(36)18(35)15(9-33)46-28/h6-7,13-16,18-26,28,33,35-40H,8-10H2,1-5H3/t13-,14-,15+,16+,18+,19-,20+,21+,22+,23+,24+,25+,26-,28+,30-,31+,32+/m0/s1
SMILES	CC(=CC(=O)O[C@@H]1[C@@H]2[C@]34CO[C@]2([C@H]([C@@H]([C@@H]4[C@]2(C)[C@@H](C[C@H]3OC1=O)C(=C[C@@H]([C@H]2O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)C)O)O)C(=O)OC)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	684.26	Volume:	638.151 ? Van der Waals volume.
Dense:	1.072	LogP:	-0.207 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.728 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.946 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	33.0
TPSA:	248.2 ? Topological Polar Surface Area.	H-Bond Acceptor:	16.0
H-Bond Donor:	7.0	Rings:	6.0
Heavy Atoms:	16.0

MedChem Properties

QED Drug-Likeness Score:	0.065	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.038	Fsp³:	0.781
MCE-18:	168.667 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.55	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.09 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.092	Promiscuous compounds:	0.33

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.944	MDCK Permeability:	-5.373
Pgp-inhibitor:	0.0	Pgp-substrate:	0.995
PAMPA:	0.996 ? 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):	0.624
20% Bioavailability (F20%):	0.227	30% Bioavailability (F30%):	0.988
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.023	MRP1:	0.894
Plasma Protein Binding (PPB):	61.445%	Volume Distribution (VD):	-0.447
Fu:	36.555% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.001
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.01	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.015
HLM stability:	0.001 ? 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):

1.237

Half-life (T1/2):

3.856

ADMET: Toxicity

hERG Blockers:	0.004	hERG Blockers (10um):	0.017
Human Hepatotoxicity (H-HT):	0.781	Drug-induced Liver Injury (DILI):	0.987
AMES Toxicity:	0.959	Rat Oral Acute Toxicity:	0.123
Maximum Recommended Daily Dose:	0.101	Skin Sensitization:	1.0
Carcinogencity:	0.13	Eye Corrosion:	0.0
Eye Irritation:	0.042	Respiratory Toxicity:	0.025
Drug-induced Neurotoxicity:	0.103	Ototoxicity:	0.972
Hematotoxicity:	0.486	Drug-induced Nephrotoxicity:	0.987
Genotoxicity:	0.949	RPMI-8226 Immunitoxicity:	0.259
A549 Cytotoxicity:	0.346	Hek293 Cytotoxicity:	0.297
BCF:	0.419 ? 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:	3.14 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.914 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.012 ? 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
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	seed	n.a.	DOI[10.1016/0031-9422(96)00258-0]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	fruit	n.a.	DOI[10.1016/S1383-5769(99)00023-9]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10086989]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1512598]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[15165151]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	fruit	Indonesia	n.a.	PMID[17896817]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	Vietnam	n.a.	PMID[19026551]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	seeds	n.a.	n.a.	PMID[20050684]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[22506620]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[6481366]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7561896]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO14948	Brucea javanica	Species	Simaroubaceae	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

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

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 NPC12557 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	19488
0.1-0.2	26364
0.2-0.3	3807
0.3-0.4	143
0.4-0.5	13
0.5-0.6	28
0.6-0.7	13
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	Natural Product ID
0.6771	Remote Similarity	NPC262813
0.6562	Remote Similarity	NPC190065
0.6364	Remote Similarity	NPC479019
0.6337	Remote Similarity	NPC251998
0.63	Remote Similarity	NPC480779
0.6263	Remote Similarity	NPC141215
0.6162	Remote Similarity	NPC596
0.6154	Remote Similarity	NPC67251
0.6139	Remote Similarity	NPC295885
0.6111	Remote Similarity	NPC480783
0.6082	Remote Similarity	NPC87662
0.6078	Remote Similarity	NPC140045
0.6022	Remote Similarity	NPC470780
0.5977	Remote Similarity	NPC470776
0.5962	Remote Similarity	NPC471089
0.5905	Remote Similarity	NPC480778
0.5876	Remote Similarity	NPC475636
0.58	Remote Similarity	NPC602216
0.5795	Remote Similarity	NPC213084
0.5795	Remote Similarity	NPC17772
0.5789	Remote Similarity	NPC480777
0.5743	Remote Similarity	NPC309096
0.5604	Remote Similarity	NPC485623
0.5591	Remote Similarity	NPC18945
0.5591	Remote Similarity	NPC152301
0.5524	Remote Similarity	NPC54614
0.5474	Remote Similarity	NPC480787
0.5474	Remote Similarity	NPC480784
0.5435	Remote Similarity	NPC89929
0.5435	Remote Similarity	NPC479018
0.5417	Remote Similarity	NPC265557
0.5368	Remote Similarity	NPC190185
0.5319	Remote Similarity	NPC146432
0.5319	Remote Similarity	NPC470778
0.5258	Remote Similarity	NPC94509
0.5204	Remote Similarity	NPC476729
0.5155	Remote Similarity	NPC480785
0.5135	Remote Similarity	NPC102465
0.5102	Remote Similarity	NPC479017
0.51	Remote Similarity	NPC480786
0.505	Remote Similarity	NPC105926

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC12557 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7073
0.1-0.2	2011
0.2-0.3	65
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