NPASS Compound

Natural Product: NPC27541

Natural Product ID	NPC27541
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1-O-Deacetyl-1-O-Tigloylohchinolide A
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL453337
PubChem CID	11239365
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids [CHEMONTID:0002380] Limonoids

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 96102 0 0 0 0 0 0 0 0999 V2000 4.6814 -2.9952 -4.1963 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1291 -2.1145 -3.1023 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8855 -1.6716 -2.1292 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3740 -0.8312 -1.0761 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1607 -0.4199 -0.1500 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0664 -0.3880 -0.9306 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6499 0.4295 0.1219 C 0 0 1 0 0 0 0 0 0 0 0 0 2.3422 1.8065 -0.4372 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2865 2.8302 0.6877 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8564 4.0742 0.2986 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5414 5.2575 0.2667 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7263 5.2085 0.6434 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8542 6.4811 -0.1981 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6020 2.2870 1.9153 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8619 1.1192 1.4759 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5536 -0.1056 0.9987 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2240 -0.8069 2.1418 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4973 -0.8814 0.2681 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0499 -1.9447 -0.5656 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1798 -3.1028 -0.8919 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6722 -4.2805 -0.7416 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1221 -3.0342 -1.3489 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9541 -1.8661 -1.1489 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8822 -1.6404 0.3126 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0585 -1.9145 0.8262 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5437 -1.8692 2.2272 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0427 -2.2857 -0.2318 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3455 -2.1062 -1.5183 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4598 -3.7050 -0.0976 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7627 -4.1545 -0.0467 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6931 -5.5095 0.0844 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4371 -5.8623 0.1116 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6510 -4.7957 0.0037 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7109 -1.1676 1.1433 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4274 -2.2570 2.1164 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2324 0.1145 1.7061 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1830 0.9291 2.4850 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5876 2.1985 2.7483 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3673 3.1115 2.3153 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5096 0.9558 0.5729 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7273 1.5877 0.4893 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5637 1.4185 1.3994 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0458 2.4395 -0.6321 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1526 2.6539 -1.6667 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4955 3.4761 -2.7151 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7345 4.0914 -2.7384 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6318 3.8827 -1.7098 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2711 3.0594 -0.6736 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4583 2.2315 3.1140 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3202 -2.0514 -2.1200 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1185 -3.8815 -3.6784 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8836 -3.3826 -4.8321 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5017 -2.5042 -4.7413 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0873 -1.8342 -3.1183 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5744 0.6454 0.7809 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4772 1.8054 -1.0895 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2142 2.0863 -1.0682 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3486 2.9403 0.9927 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7422 7.1858 0.6623 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3822 6.9926 -1.0289 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8265 6.2529 -0.5456 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3056 1.4788 0.5376 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6579 -0.8824 3.0662 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0993 -0.1325 2.4153 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7395 -1.7417 1.8734 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0676 -0.1027 -0.4498 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0249 -2.3639 -0.2436 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2854 -1.5605 -1.6252 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4214 -1.0435 -1.6473 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8294 -1.9857 3.0218 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2110 -2.7863 2.3542 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2716 -1.0391 2.3160 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9564 -1.6248 -0.1423 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7576 -1.1946 -2.0349 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5069 -2.9322 -2.2527 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6441 -3.5428 -0.1012 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5113 -6.2279 0.1588 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5867 -4.8757 0.0059 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5940 -2.7291 1.9898 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4528 -1.9575 3.1857 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0746 -3.1773 1.9515 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0996 0.1083 2.3225 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0545 0.3148 3.3672 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0562 3.6195 1.4186 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6335 3.8622 3.0777 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1854 2.1610 -1.6276 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8065 3.6570 -3.5397 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0267 4.7433 -3.5527 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5930 4.3822 -1.7635 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9838 2.9021 0.1289 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1641 1.5137 3.8778 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5632 2.1688 2.8771 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3914 3.2434 3.6238 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6011 -2.7023 -2.9571 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9513 -1.1395 -2.1838 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5708 -2.6019 -1.1884 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 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 2 0 11 13 1 0 9 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 2 0 20 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 25 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 1 0 24 34 1 0 34 35 1 1 34 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 36 40 1 0 40 41 1 0 41 42 2 0 41 43 1 0 43 44 2 0 44 45 1 0 45 46 2 0 46 47 1 0 47 48 2 0 14 49 1 1 3 50 1 0 16 7 1 0 34 18 1 0 48 43 1 0 39 14 1 0 37 15 1 0 28 23 1 0 33 29 2 0 1 51 1 0 1 52 1 0 1 53 1 0 2 54 1 0 7 55 1 1 8 56 1 0 8 57 1 0 9 58 1 1 13 59 1 0 13 60 1 0 13 61 1 0 15 62 1 6 17 63 1 0 17 64 1 0 17 65 1 0 18 66 1 6 19 67 1 0 19 68 1 0 23 69 1 6 26 70 1 0 26 71 1 0 26 72 1 0 27 73 1 6 28 74 1 0 28 75 1 0 30 76 1 0 31 77 1 0 33 78 1 0 35 79 1 0 35 80 1 0 35 81 1 0 36 82 1 1 37 83 1 1 39 84 1 0 39 85 1 0 44 86 1 0 45 87 1 0 46 88 1 0 47 89 1 0 48 90 1 0 49 91 1 0 49 92 1 0 49 93 1 0 50 94 1 0 50 95 1 0 50 96 1 0 M END

Standard InCHIKey	YEENTMJDONCLMX-MSEKIEPGSA-N
Standard InCHI	InChI=1S/C40H46O10/c1-8-21(2)36(43)49-30-18-29(47-23(4)41)38(5)20-46-33-34(38)39(30,6)28-17-31(42)48-27-16-26(25-14-15-45-19-25)22(3)32(27)40(28,7)35(33)50-37(44)24-12-10-9-11-13-24/h8-15,19,26-30,33-35H,16-18,20H2,1-7H3/b21-8+/t26-,27+,28-,29-,30+,33-,34+,35-,38-,39+,40-/m1/s1
SMILES	C/C=C(/C(=O)O[C@H]1C[C@@H](OC(=O)C)[C@@]2([C@H]3[C@@]1(C)[C@H]1CC(=O)O[C@@H]4C(=C(C)[C@@H](C4)c4ccoc4)[C@]1(C)[C@@H]([C@@H]3OC2)OC(=O)c1ccccc1)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	686.31	Volume:	699.402 ? Van der Waals volume.
Dense:	0.981	LogP:	3.321 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.271 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.618 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	40.0
TPSA:	127.57 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	0.0	Rings:	7.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.144	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.579	Fsp³:	0.55
MCE-18:	163.742 ? 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:	0.989	Fluc inhibitor:	0.025 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.016 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.007 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.074	Promiscuous compounds:	0.106

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.085	MDCK Permeability:	-4.75
Pgp-inhibitor:	0.988	Pgp-substrate:	0.802
PAMPA:	0.331 ? 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%):	0.134	30% Bioavailability (F30%):	0.495
50% Bioavailability (F50%):	0.813

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	1.0
Plasma Protein Binding (PPB):	95.256%	Volume Distribution (VD):	-0.25
Fu:	5.464% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.986
OATP1B3 inhibitor:	0.473	BCRP inhibitor:	0.003
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.125
CYP2C19-inhibitor:	0.02	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.027
CYP3A4-inhibitor:	0.104	CYP3A4-substrate:	0.005
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.996 ? 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):

7.478

Half-life (T1/2):

0.623

ADMET: Toxicity

hERG Blockers:	0.055	hERG Blockers (10um):	0.218
Human Hepatotoxicity (H-HT):	0.683	Drug-induced Liver Injury (DILI):	0.995
AMES Toxicity:	0.671	Rat Oral Acute Toxicity:	0.857
Maximum Recommended Daily Dose:	0.985	Skin Sensitization:	0.996
Carcinogencity:	0.917	Eye Corrosion:	0.0
Eye Irritation:	0.006	Respiratory Toxicity:	0.406
Drug-induced Neurotoxicity:	0.741	Ototoxicity:	0.554
Hematotoxicity:	0.555	Drug-induced Nephrotoxicity:	0.998
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.17
A549 Cytotoxicity:	0.915	Hek293 Cytotoxicity:	0.29
BCF:	0.829 ? 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:	3.785 ? 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:	5.055 ? 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
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	Brazilian	n.a.	PMID[15387656]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	ripe fruit	n.a.	PMID[16205005]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[33253570]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36362399]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[3701342]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO18932	Melia azedarach	Species	Meliaceae	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	1

Activity Type	# Activity
Organism	1
Non-molecular	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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	29700.0	nM	PMID[15387656]
NPT140	Organism	Artemia	Artemia	Activity	=	100.0	%	PMID[22804108]

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 NPC27541 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	13373
0.1-0.2	34162
0.2-0.3	2048
0.3-0.4	225
0.4-0.5	24
0.5-0.6	15
0.6-0.7	4
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9268	High Similarity	NPC62692
0.9176	High Similarity	NPC126984
0.8434	Intermediate Similarity	NPC29695
0.8313	Intermediate Similarity	NPC182427
0.764	Intermediate Similarity	NPC308205
0.7312	Intermediate Similarity	NPC118086
0.7174	Intermediate Similarity	NPC488535
0.6735	Remote Similarity	NPC61967
0.6596	Remote Similarity	NPC322546
0.6489	Remote Similarity	NPC475066
0.6237	Remote Similarity	NPC604850
0.5941	Remote Similarity	NPC608643
0.59	Remote Similarity	NPC214495
0.59	Remote Similarity	NPC470119
0.5859	Remote Similarity	NPC610307
0.5842	Remote Similarity	NPC608851
0.5673	Remote Similarity	NPC475641
0.566	Remote Similarity	NPC11062
0.5577	Remote Similarity	NPC307781
0.5577	Remote Similarity	NPC472670
0.5577	Remote Similarity	NPC264690
0.5577	Remote Similarity	NPC601577
0.5437	Remote Similarity	NPC475226
0.5385	Remote Similarity	NPC472671
0.5152	Remote Similarity	NPC601664
0.5048	Remote Similarity	NPC470792

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC27541 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3216
0.1-0.2	5879
0.2-0.3	55
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