NPASS Compound

Natural Product: NPC478451

Natural Product ID	NPC478451
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	BLSJJGBHGVBYHF-XYHBIZDZSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	71450688
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002650] Diarylheptanoids [CHEMONTID:0002651] Linear diarylheptanoids [CHEMONTID:0000356] Curcuminoids

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 87 89 0 0 0 0 0 0 0 0999 V2000 -10.5903 1.6509 0.9945 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.8263 0.7027 -0.1208 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.7887 0.1663 -0.7393 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3820 0.5080 -0.3223 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6461 1.1115 -1.4586 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2431 1.5011 -1.1775 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.7003 2.2153 -2.4831 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3211 0.3070 -1.0886 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.5618 -0.7196 -0.1115 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0174 -0.7868 1.0786 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0644 0.2646 1.4833 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.7900 1.4805 1.9650 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1823 0.5884 0.2828 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9235 0.8507 -0.9750 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3389 -0.5144 0.0830 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9609 -0.5241 0.1348 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1671 0.5771 0.3388 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2262 0.4664 0.3717 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8571 -0.7404 0.2026 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3068 -0.7695 0.2156 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0233 -1.8703 0.0964 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5166 -1.7997 0.1169 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2672 -2.8551 0.0096 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6334 -3.0884 -0.0078 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8795 -4.4226 -0.1135 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8747 -2.3882 0.0443 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1919 -1.1222 0.1278 C 0 0 0 0 0 0 0 0 0 0 0 0 10.5557 -0.5930 0.1683 C 0 0 0 0 0 0 0 0 0 0 0 0 11.7056 -1.3255 0.1415 C 0 0 0 0 0 0 0 0 0 0 0 0 12.9692 -0.7135 0.1615 C 0 0 0 0 0 0 0 0 0 0 0 0 13.0943 0.6536 0.2095 C 0 0 0 0 0 0 0 0 0 0 0 0 11.9343 1.4199 0.2381 C 0 0 0 0 0 0 0 0 0 0 0 0 10.6955 0.7988 0.2177 C 0 0 0 0 0 0 0 0 0 0 0 0 12.1115 2.7909 0.2853 O 0 0 0 0 0 0 0 0 0 0 0 0 10.9961 3.6558 0.3162 C 0 0 0 0 0 0 0 0 0 0 0 0 14.3391 1.2854 0.2299 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1201 -0.5828 0.2552 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0479 -1.8288 0.0020 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3101 -1.7680 -0.0377 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1355 -2.8591 -0.2389 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7383 -4.1781 -0.4324 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2641 -0.2583 2.5164 O 0 0 0 0 0 0 0 0 0 0 0 0 -12.1926 0.3564 -0.5487 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.5714 2.0451 1.3791 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0413 2.5555 0.6643 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0234 1.1845 1.8290 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9565 -0.5199 -1.5452 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9550 -0.3812 0.0882 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4792 1.2752 0.5015 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7174 0.3717 -2.3066 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1680 2.0140 -1.8671 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1065 2.2301 -0.3846 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0239 1.5557 -3.0211 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5660 2.4548 -3.1266 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1838 3.1328 -2.1954 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3757 -0.1331 -2.1479 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2218 -1.5743 -0.3666 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2540 -1.6066 1.7826 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8982 1.3737 1.8377 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4791 2.4133 1.4585 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6220 1.5801 3.0656 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5300 1.4603 0.5661 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2991 0.4452 -1.8203 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8948 1.9681 -1.1377 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6354 1.5381 0.4716 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8089 1.3590 0.5346 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8959 0.1516 0.3324 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5745 -2.8223 -0.0131 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6133 -3.7928 -0.0949 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8390 -3.0097 0.0089 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3987 -0.4242 0.1644 H 0 0 0 0 0 0 0 0 0 0 0 0 11.6477 -2.4087 0.1037 H 0 0 0 0 0 0 0 0 0 0 0 0 13.8340 -1.3588 0.1373 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8114 1.4254 0.2423 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2793 4.6816 -0.0732 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1446 3.3386 -0.2880 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6339 3.8569 1.3641 H 0 0 0 0 0 0 0 0 0 0 0 0 14.9368 1.3551 -0.5842 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8048 0.0222 1.0244 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5241 -2.7859 -0.1327 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7882 -4.4151 -1.5129 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5138 -4.8359 0.0621 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2245 -4.4497 0.0369 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2014 0.4467 3.2304 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.1914 -0.7299 -0.8450 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.9524 0.4281 0.2570 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.5233 0.9414 -1.4474 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 1 0 5 6 1 0 6 7 1 0 6 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 11 13 1 0 13 14 1 0 13 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 32 34 1 0 34 35 1 0 31 36 1 0 22 37 1 0 19 38 1 0 38 39 2 0 39 40 1 0 40 41 1 0 11 42 1 1 2 43 1 0 14 8 1 0 39 16 1 0 33 28 1 0 1 44 1 0 1 45 1 0 1 46 1 0 3 47 1 0 4 48 1 0 4 49 1 0 5 50 1 0 5 51 1 0 6 52 1 1 7 53 1 0 7 54 1 0 7 55 1 0 8 56 1 6 9 57 1 0 10 58 1 0 12 59 1 0 12 60 1 0 12 61 1 0 13 62 1 1 14 63 1 0 14 64 1 0 17 65 1 0 18 66 1 0 20 67 1 0 21 68 1 0 23 69 1 0 26 70 1 0 27 71 1 0 29 72 1 0 30 73 1 0 33 74 1 0 35 75 1 0 35 76 1 0 35 77 1 0 36 78 1 0 37 79 1 0 38 80 1 0 41 81 1 0 41 82 1 0 41 83 1 0 42 84 1 0 43 85 1 0 43 86 1 0 43 87 1 0 M END

Standard InCHIKey	BLSJJGBHGVBYHF-XYHBIZDZSA-N
Standard InCHI	InChI=1S/C36H44O7/c1-24(2)8-7-9-25(3)28-18-19-36(4,40)35(22-28)43-32-17-13-27(21-34(32)42-6)11-15-30(38)23-29(37)14-10-26-12-16-31(39)33(20-26)41-5/h8,10-21,23,25,28,35,38-40H,7,9,22H2,1-6H3/b14-10+,15-11+,30-23-/t25-,28+,35-,36+/m0/s1
SMILES	CC(=CCC[C@H](C)[C@@H]1C=C[C@](C)([C@H](C1)Oc1ccc(/C=C/C(=C/C(=O)/C=C/c2ccc(c(c2)OC)O)/O)cc1OC)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	588.31	Volume:	635.437 ? Van der Waals volume.
Dense:	0.926	LogP:	5.676 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.118 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.799 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	23.0
TPSA:	105.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.096	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.57	Fsp³:	0.361
MCE-18:	75.918 ? 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:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.986	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.056 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.656 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.444	Promiscuous compounds:	0.225

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.196	MDCK Permeability:	-4.831
Pgp-inhibitor:	0.978	Pgp-substrate:	0.0
PAMPA:	0.083 ? 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%):	0.974	30% Bioavailability (F30%):	0.989
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.0
Plasma Protein Binding (PPB):	96.811%	Volume Distribution (VD):	-0.213
Fu:	2.51% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.957
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.567
CYP2C19-inhibitor:	0.213	CYP2C19-substrate:	0.005
CYP2C9-inhibitor:	0.163	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.995	CYP2D6-substrate:	0.809
CYP3A4-inhibitor:	0.111	CYP3A4-substrate:	0.839
CYP2B6-substrate:	0.004	CYP2C8-inhibitor:	1.0
HLM stability:	0.971 ? 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):

6.794

Half-life (T1/2):

1.078

ADMET: Toxicity

hERG Blockers:	0.122	hERG Blockers (10um):	0.093
Human Hepatotoxicity (H-HT):	0.769	Drug-induced Liver Injury (DILI):	0.788
AMES Toxicity:	0.19	Rat Oral Acute Toxicity:	0.218
Maximum Recommended Daily Dose:	0.65	Skin Sensitization:	0.893
Carcinogencity:	0.432	Eye Corrosion:	0.001
Eye Irritation:	0.758	Respiratory Toxicity:	0.819
Drug-induced Neurotoxicity:	0.293	Ototoxicity:	0.664
Hematotoxicity:	0.233	Drug-induced Nephrotoxicity:	0.929
Genotoxicity:	0.269	RPMI-8226 Immunitoxicity:	0.138
A549 Cytotoxicity:	0.178	Hek293 Cytotoxicity:	0.219
BCF:	1.659 ? 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:	4.619 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.09 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.566 ? 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
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12350137]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	rhizome	n.a.	n.a.	PMID[12617587]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	Rhizomes	n.a.	n.a.	PMID[23153397]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	leaf	n.a.	PMID[23901173]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28068085]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9584408]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	Essential Oil	n.a.	n.a.	Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	Rhizome	n.a.	n.a.	Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	Rhizome Essent. Oil	n.a.	n.a.	Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	Root	n.a.	n.a.	Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.		Database[Phenol-Explorer]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO24124	Curcuma longa	Species	Zingiberaceae	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	3

Activity Type	# Activity
Cell line	3

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
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	24600.0	nM	PMID[23153397]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	29500.0	nM	PMID[23153397]
NPT81	Cell line	A549	Homo sapiens	IC50	=	35000.0	nM	PMID[23153397]

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 NPC478451 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	7224
0.1-0.2	38814
0.2-0.3	3562
0.3-0.4	233
0.4-0.5	12
0.5-0.6	6
0.6-0.7	4
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8554	High Similarity	NPC478450
0.7303	Intermediate Similarity	NPC478449
0.7033	Intermediate Similarity	NPC478452
0.6923	Remote Similarity	NPC478453
0.6277	Remote Similarity	NPC478448
0.6105	Remote Similarity	NPC478444
0.6076	Remote Similarity	NPC269843
0.5833	Remote Similarity	NPC478446
0.5729	Remote Similarity	NPC478447
0.5513	Remote Similarity	NPC109083
0.5432	Remote Similarity	NPC189844
0.5306	Remote Similarity	NPC478443
0.5149	Remote Similarity	NPC478445

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC478451 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3341
0.1-0.2	5708
0.2-0.3	98
0.3-0.4	3
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