NPASS Compound

Natural Product: NPC241016

Natural Product ID	NPC241016
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	FDHNLHLOJLLXDH-JIYHLSBYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	6436550
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides

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 80 83 0 0 0 0 0 0 0 0999 V2000 -8.0886 0.3113 -2.0250 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7857 0.9980 -0.7125 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.9499 1.8890 -0.2757 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.7232 2.1649 1.2059 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.2459 2.0372 1.5538 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.6987 0.6767 1.2237 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.4747 0.7224 0.5908 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4784 0.0262 1.2701 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2058 0.1869 0.4277 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4846 -0.1586 -0.9989 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4212 -1.6366 -1.2878 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4845 -2.3433 -0.3303 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4500 -1.2866 0.0895 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3574 -1.8490 0.7194 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9434 -1.8112 0.2832 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3937 -1.2035 -0.8654 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7289 -1.2181 -1.2237 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6579 -1.8601 -0.4130 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0451 -1.8447 -0.8365 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4400 -2.7890 -1.5732 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9456 -0.7965 -0.4370 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1906 -0.8154 -0.8383 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1732 0.2102 -0.4793 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4689 0.1020 -0.9546 C 0 0 0 0 0 0 0 0 0 0 0 0 10.4043 1.0477 -0.6327 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0981 2.1246 0.1626 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8021 2.2250 0.6329 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8450 1.2761 0.3156 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4905 3.3094 1.4346 O 0 0 0 0 0 0 0 0 0 0 0 0 11.0695 3.0501 0.4601 O 0 0 0 0 0 0 0 0 0 0 0 0 12.3731 2.9163 -0.0343 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2403 -2.4710 0.7316 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9140 -2.4367 1.0542 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1989 -3.1069 1.5235 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7430 -3.7347 2.7075 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1255 -0.5805 -2.4071 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1286 -0.4536 0.9793 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8351 -3.4076 -0.9624 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6784 -2.2266 -1.2950 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7199 0.5852 -1.8988 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5995 0.0744 0.3188 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1290 2.3337 2.9133 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.3890 1.2056 1.9979 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.0003 3.0536 -1.0172 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6716 -0.6221 -1.8566 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1187 0.0381 -2.4927 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5889 1.0231 -2.6829 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9096 1.6754 -0.8219 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9031 1.3111 -0.3949 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0292 3.1833 1.4869 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7344 2.8480 0.9641 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6420 0.0820 2.1664 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7843 -1.0143 1.3652 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3190 0.4379 2.2845 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9877 1.2898 0.4609 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5539 0.1471 -1.2012 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9439 -1.7360 -2.3040 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9964 -2.7599 0.5493 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1588 -0.7877 -0.8305 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7116 -0.6930 -1.5264 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5886 -0.0060 0.1880 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5529 -1.6280 -1.4794 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7436 -0.7239 -1.5769 H 0 0 0 0 0 0 0 0 0 0 0 0 11.4065 0.9258 -1.0251 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8493 1.4241 0.7230 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9114 3.3918 2.3525 H 0 0 0 0 0 0 0 0 0 0 0 0 12.9247 3.8523 0.2651 H 0 0 0 0 0 0 0 0 0 0 0 0 12.4203 2.8073 -1.1346 H 0 0 0 0 0 0 0 0 0 0 0 0 12.8910 2.0310 0.4336 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6079 -2.9308 1.9709 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8904 -4.4273 2.5059 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5450 -4.3475 3.1548 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3456 -2.9648 3.4110 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8404 0.3866 -2.5894 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2989 -3.8581 -0.2516 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7665 -2.7622 -2.1215 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8852 1.5453 -1.6524 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7866 3.0266 3.1812 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5964 1.6017 2.8767 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5173 3.7372 -0.5226 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 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 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 27 29 1 0 26 30 1 0 30 31 1 0 18 32 1 0 32 33 2 0 32 34 1 0 34 35 1 0 17 36 1 0 13 37 1 0 12 38 1 0 11 39 1 0 10 40 1 0 6 41 1 0 5 42 1 0 4 43 1 0 3 44 1 0 41 2 1 0 37 9 1 0 33 15 1 0 28 23 1 0 1 45 1 0 1 46 1 0 1 47 1 0 2 48 1 6 3 49 1 1 4 50 1 1 5 51 1 6 6 52 1 1 8 53 1 0 8 54 1 0 9 55 1 6 10 56 1 6 11 57 1 6 12 58 1 1 13 59 1 6 16 60 1 0 21 61 1 0 22 62 1 0 24 63 1 0 25 64 1 0 28 65 1 0 29 66 1 0 31 67 1 0 31 68 1 0 31 69 1 0 33 70 1 0 35 71 1 0 35 72 1 0 35 73 1 0 36 74 1 0 38 75 1 0 39 76 1 0 40 77 1 0 42 78 1 0 43 79 1 0 44 80 1 0 M END

Standard InCHIKey	FDHNLHLOJLLXDH-JIYHLSBYSA-N
Standard InCHI	InChI=1S/C29H36O15/c1-12-22(33)24(35)26(37)28(42-12)41-11-20-23(34)25(36)27(38)29(44-20)43-14-9-17(32)21(19(10-14)40-3)15(30)6-4-13-5-7-18(39-2)16(31)8-13/h4-10,12,20,22-29,31-38H,11H2,1-3H3/b6-4+/t12-,20+,22-,23+,24+,25-,26+,27+,28+,29+/m0/s1
SMILES	C[C@H]1[C@@H]([C@H]([C@H]([C@H](OC[C@@H]2[C@H]([C@@H]([C@H]([C@H](Oc3cc(c(C(=O)/C=C/c4ccc(c(c4)O)OC)c(c3)OC)O)O2)O)O)O)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	624.21	Volume:	586.676 ? Van der Waals volume.
Dense:	1.064	LogP:	0.089 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.83 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.197 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	26.0
TPSA:	234.29 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	8.0	Rings:	4.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.117	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.683	Fsp³:	0.483
MCE-18:	103.953 ? 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:	0.672	Fluc inhibitor:	0.797 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.31 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.623 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.094	Promiscuous compounds:	0.421

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.083	MDCK Permeability:	-5.32
Pgp-inhibitor:	0.003	Pgp-substrate:	0.254
PAMPA:	0.944 ? 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):	0.345
20% Bioavailability (F20%):	0.17	30% Bioavailability (F30%):	0.961
50% Bioavailability (F50%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.002
Plasma Protein Binding (PPB):	81.803%	Volume Distribution (VD):	-0.22
Fu:	15.794% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.291
BSEP inhibitor:	0.066

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	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:	0.0	CYP3A4-substrate:	0.989
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.003 ? 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):

1.383

Half-life (T1/2):

4.349

ADMET: Toxicity

hERG Blockers:	0.041	hERG Blockers (10um):	0.2
Human Hepatotoxicity (H-HT):	0.377	Drug-induced Liver Injury (DILI):	0.772
AMES Toxicity:	0.806	Rat Oral Acute Toxicity:	0.003
Maximum Recommended Daily Dose:	0.01	Skin Sensitization:	0.968
Carcinogencity:	0.013	Eye Corrosion:	0.0
Eye Irritation:	0.068	Respiratory Toxicity:	0.003
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.972
Hematotoxicity:	0.134	Drug-induced Nephrotoxicity:	0.799
Genotoxicity:	0.031	RPMI-8226 Immunitoxicity:	0.315
A549 Cytotoxicity:	0.3	Hek293 Cytotoxicity:	0.313
BCF:	0.53 ? 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:	3.199 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.813 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.063 ? 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
NPO19584	Pericarpium citri reticulatae	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19584	Pericarpium citri reticulatae	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]

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	22
Flu intensity	4
Inhibition	7
Ratio	1
mortality	5

Activity Type	# Activity
Individual protein	6
Cell line	18
Single protein	5
Organism	9
No target	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3902	Individual protein	Acetylcholinesterase	Mus musculus	Activity	=	0.0	U	PMID[38016411]
NPT5337	Individual protein	Butyrylcholinesterase	Mus musculus	Activity	=	0.0	U	PMID[38016411]
NPT30107	Single protein	Amyloid-beta A4 protein	Homo sapiens	Flu intensity	=	10.0	a.u.	PMID[38016411]
NPT30107	Single protein	Amyloid-beta A4 protein	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[38016411]
NPT30107	Single protein	Amyloid-beta A4 protein	Homo sapiens	Flu intensity	=	19.8	a.u.	PMID[38016411]
NPT30107	Single protein	Amyloid-beta A4 protein	Homo sapiens	Flu intensity	=	11.81	a.u.	PMID[38016411]
NPT66	Individual protein	Acetylcholinesterase	Electrophorus electricus	Inhibition	>	80.0	%	PMID[38016411]
NPT30107	Single protein	Amyloid-beta A4 protein	Homo sapiens	Flu intensity	=	6.45	a.u.	PMID[38016411]
NPT66	Individual protein	Acetylcholinesterase	Electrophorus electricus	Inhibition	=	93.04	%	PMID[38016411]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3908	Cell line	N2a	Mus musculus	Activity	=	99.6	%	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Activity	n.a.	n.a.	n.a.	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Activity	=	77.84	nmol	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Activity	=	64.63	nmol	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Activity	=	81.66	%	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Inhibition	n.a.	n.a.	%	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Activity	=	33.91	mmol	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Activity	=	3.97	mmol	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Activity	=	27.87	mmol	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Activity	=	0.07	mM/min	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Activity	=	0.03	mM/min	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Activity	=	70.33	%	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Ratio	=	0.51	n.a.	PMID[38016411]
NPT3908	Cell line	N2a	Mus musculus	Activity	=	6.1	mmol	PMID[38016411]
NPT28833	No target	No relevant target	n.a.	Inhibition	=	68.43	%	PMID[38016411]
NPT176	Organism	Artemia salina	Artemia salina	Activity	n.a.	n.a.	n.a.	PMID[38016411]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT176	Organism	Artemia salina	Artemia salina	mortality	=	0.0	%	PMID[38016411]
NPT176	Organism	Artemia salina	Artemia salina	mortality	=	3.33	%	PMID[38016411]
NPT176	Organism	Artemia salina	Artemia salina	mortality	=	53.33	%	PMID[38016411]
NPT176	Organism	Artemia salina	Artemia salina	mortality	=	36.6	%	PMID[38016411]

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
-	Artemia salina	LC50	=	100.0	ug.mL-1	PMID[38016411]

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 NPC241016 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	14932
0.1-0.2	29204
0.2-0.3	4797
0.3-0.4	786
0.4-0.5	124
0.5-0.6	12
0.6-0.7	3
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
0.6742	Remote Similarity	NPC44328
0.6742	Remote Similarity	NPC79056
0.6087	Remote Similarity	NPC43587
0.5875	Remote Similarity	NPC469622
0.587	Remote Similarity	NPC271270
0.5789	Remote Similarity	NPC293629
0.5698	Remote Similarity	NPC488085
0.5455	Remote Similarity	NPC3293
0.5385	Remote Similarity	NPC229687
0.5281	Remote Similarity	NPC40664
0.5281	Remote Similarity	NPC197723
0.5116	Remote Similarity	NPC469621
0.5116	Remote Similarity	NPC479450
0.5111	Remote Similarity	NPC310064
0.5106	Remote Similarity	NPC212748

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC241016 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4389
0.1-0.2	4662
0.2-0.3	89
0.3-0.4	7
0.4-0.5	2
0.5-0.6	0
0.6-0.7	1
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
0.6742	Remote Similarity	NPD7074	Phase 3

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