NPASS Compound

Natural Product: NPC476382

Natural Product ID	NPC476382
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(2R,3R,4R,5R,6R)-5-Hydroxy-2-(Hydroxymethyl)-6-[2-(4-Hydroxyphenyl)Ethoxy]-4-[[(2S,3R,4R,5R,6S)-3,4,5-Trihydroxy-6-Methyloxan-2-Yl]Methoxy]Oxan-3-Yl] (E)-3-(4-Hydroxy-3-Methoxyphenyl)Prop-2-Enoate
IUPAC Name	[(2R,3R,4R,5R,6R)-5-hydroxy-2-(hydroxymethyl)-6-[2-(4-hydroxyphenyl)ethoxy]-4-[[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]methoxy]oxan-3-yl] (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate
Synonyms	Syringalide A 3'-O-Rha
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL590396
PubChem CID	46228755
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0000059] Coumaric acids and derivatives

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 85 88 0 0 0 0 0 0 0 0999 V2000 -2.1448 -4.6866 -3.5025 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4558 -3.4882 -2.6215 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2053 -4.0204 -1.4059 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6223 -3.2745 -0.2023 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5761 -1.8031 -0.6660 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5073 -1.5950 -1.6748 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2723 -2.9117 -2.2217 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1959 -1.0479 -1.2699 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0266 0.1701 -0.7723 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4339 0.6378 0.3958 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2729 1.8906 0.1723 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1081 2.8712 1.2837 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8417 2.2650 2.5090 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3879 1.6347 2.5390 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7998 1.0464 1.2363 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5026 -0.1542 1.4871 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8534 -0.3435 1.0543 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2830 0.6488 0.4615 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4364 -1.5930 1.3737 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5669 -2.1575 1.2095 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8196 -1.7706 0.6091 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7594 -2.7696 0.3440 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9828 -2.4745 -0.1728 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3666 -1.1899 -0.4628 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4726 -0.2035 -0.2137 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2148 -0.4879 0.3160 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6302 -0.9629 -0.9885 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8815 -3.5169 -0.4170 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5454 -4.8624 -0.1391 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3401 0.5969 3.6366 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6806 -0.3015 3.3352 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3031 3.5615 1.4447 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1052 4.9236 1.2835 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3483 5.7303 1.4505 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3855 5.3505 0.4585 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4601 5.9779 -0.7542 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4217 5.6491 -1.7101 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3412 4.6581 -1.4447 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2653 4.0229 -0.2161 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3018 4.3572 0.7336 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3088 4.3021 -2.3634 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5849 1.5068 0.0100 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8619 -1.6356 -1.2861 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3742 -3.7227 0.1486 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0744 -5.3806 -1.2705 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7276 -4.3359 -4.4729 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3973 -5.3502 -3.0433 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0523 -5.2958 -3.7107 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0726 -2.7487 -3.1591 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2558 -3.6998 -1.4917 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3184 -3.3122 0.6488 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6057 -1.1892 0.2121 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9364 -1.0637 -2.5799 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3768 -1.8384 -0.6532 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4517 -1.0857 -2.2329 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9508 -0.0865 1.0304 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9518 2.4076 -0.7745 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3215 3.6374 1.0455 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1308 2.4012 2.8893 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4568 1.7376 0.6812 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7122 -2.3195 1.9336 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6467 -3.2305 1.6529 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4873 -3.8195 0.5573 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7248 0.8440 -0.4255 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5693 0.3417 0.5223 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7192 -0.2406 -1.6839 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1767 -4.9086 0.9179 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4885 -5.4609 -0.2013 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8009 -5.2669 -0.8430 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3049 0.0656 3.7588 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0309 1.1083 4.5887 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7077 -1.0732 3.9559 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3350 5.3237 1.9783 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7070 5.1549 0.2546 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1103 6.8018 1.4216 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7463 5.5188 2.4679 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7711 6.7625 -1.0219 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4931 6.1316 -2.6651 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9681 3.2417 0.0273 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2304 3.8736 1.6893 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3720 4.8298 -3.2272 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1985 1.9369 0.6791 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7693 -0.8097 -1.8137 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4663 -4.6607 0.4426 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9751 -5.7696 -1.0721 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 6 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 1 0 17 18 2 0 17 19 1 0 19 20 2 3 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 24 27 1 0 23 28 1 0 28 29 1 0 14 30 1 0 30 31 1 0 12 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 2 0 38 39 1 0 39 40 2 0 38 41 1 0 11 42 1 0 5 43 1 0 4 44 1 0 3 45 1 0 7 2 1 0 15 10 1 0 26 21 1 0 40 35 1 0 1 46 1 0 1 47 1 0 1 48 1 0 2 49 1 0 3 50 1 0 4 51 1 0 5 52 1 0 6 53 1 0 8 54 1 0 8 55 1 0 10 56 1 0 11 57 1 0 12 58 1 0 14 59 1 0 15 60 1 0 19 61 1 0 20 62 1 0 22 63 1 0 25 64 1 0 26 65 1 0 27 66 1 0 29 67 1 0 29 68 1 0 29 69 1 0 30 70 1 0 30 71 1 0 31 72 1 0 33 73 1 0 33 74 1 0 34 75 1 0 34 76 1 0 36 77 1 0 37 78 1 0 39 79 1 0 40 80 1 0 41 81 1 0 42 82 1 0 43 83 1 0 44 84 1 0 45 85 1 0 M END

Standard InCHIKey	VCVDCGNCACPEQN-MXIJRSCASA-N
Standard InCHI	InChI=1S/C31H40O14/c1-16-25(36)27(38)26(37)23(43-16)15-42-30-28(39)31(41-12-11-17-3-7-19(33)8-4-17)44-22(14-32)29(30)45-24(35)10-6-18-5-9-20(34)21(13-18)40-2/h3-10,13,16,22-23,25-34,36-39H,11-12,14-15H2,1-2H3/b10-6+/t16-,22+,23-,25-,26-,27+,28+,29+,30+,31+/m0/s1
SMILES	CC1C(C(C(C(O1)COC2C(C(OC(C2OC(=O)C=CC3=CC(=C(C=C3)O)OC)CO)OCCC4=CC=C(C=C4)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	636.24	Volume:	612.478 ? Van der Waals volume.
Dense:	1.039	LogP:	0.532 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.015 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.677 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	26.0
TPSA:	214.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.117	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.675	Fsp³:	0.516
MCE-18:	95.915 ? 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:	0.389	Fluc inhibitor:	0.618 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.151 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.888 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.157	Promiscuous compounds:	0.362

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.259	MDCK Permeability:	-5.29
Pgp-inhibitor:	0.0	Pgp-substrate:	0.984
PAMPA:	1.0 ? 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):	0.985
20% Bioavailability (F20%):	0.892	30% Bioavailability (F30%):	0.98
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.886
Plasma Protein Binding (PPB):	67.451%	Volume Distribution (VD):	-0.413
Fu:	34.045% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.018
OATP1B3 inhibitor:	0.984	BCRP inhibitor:	0.322
BSEP inhibitor:	0.067

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.643	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.978	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.087	CYP2D6-substrate:	0.026
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.016
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.931
HLM stability:	0.929 ? 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):

3.021

Half-life (T1/2):

2.824

ADMET: Toxicity

hERG Blockers:	0.122	hERG Blockers (10um):	0.623
Human Hepatotoxicity (H-HT):	0.443	Drug-induced Liver Injury (DILI):	0.146
AMES Toxicity:	0.833	Rat Oral Acute Toxicity:	0.183
Maximum Recommended Daily Dose:	0.213	Skin Sensitization:	0.901
Carcinogencity:	0.05	Eye Corrosion:	0.0
Eye Irritation:	0.006	Respiratory Toxicity:	0.019
Drug-induced Neurotoxicity:	0.341	Ototoxicity:	0.971
Hematotoxicity:	0.021	Drug-induced Nephrotoxicity:	0.163
Genotoxicity:	0.082	RPMI-8226 Immunitoxicity:	0.118
A549 Cytotoxicity:	0.269	Hek293 Cytotoxicity:	0.918
BCF:	0.578 ? 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:	3.093 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.956 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.965 ? 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
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	fresh stems	n.a.	n.a.	PMID[20159656]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	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
Inhibition	8
IC50	1

Activity Type	# Activity
Cell line	9

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
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	9.7	%	PMID[25871261]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	21.4	%	DOI[10.6019/CHEMBL1201861]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	35.7	%	PMID[25127165]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	55.7	%	PMID[16933872]
NPT993	Cell line	Hepatocyte	Mus musculus	IC50	=	71200.0	nM	PMID[25856683]
NPT1460	Cell line	L929	Mus musculus	Inhibition	=	4.5	%	PMID[22671987]
NPT1460	Cell line	L929	Mus musculus	Inhibition	=	4.6	%	PubChem BioAssay data set
NPT1460	Cell line	L929	Mus musculus	Inhibition	=	13.3	%	PMID[15787444]
NPT1460	Cell line	L929	Mus musculus	Inhibition	=	22.2	%	DrugMatrix in vitro pharmacology data

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 NPC476382 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	13909
0.1-0.2	31131
0.2-0.3	4137
0.3-0.4	557
0.4-0.5	87
0.5-0.6	20
0.6-0.7	15
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
0.7426	Intermediate Similarity	NPC476386
0.7204	Intermediate Similarity	NPC34587
0.6979	Remote Similarity	NPC100998
0.6979	Remote Similarity	NPC34927
0.6733	Remote Similarity	NPC476381
0.6569	Remote Similarity	NPC476380
0.6522	Remote Similarity	NPC46137
0.6346	Remote Similarity	NPC471062
0.6226	Remote Similarity	NPC306890
0.6224	Remote Similarity	NPC476385
0.6214	Remote Similarity	NPC476384
0.6168	Remote Similarity	NPC94871
0.6168	Remote Similarity	NPC473427
0.6122	Remote Similarity	NPC263829
0.61	Remote Similarity	NPC252292
0.6038	Remote Similarity	NPC470933
0.6019	Remote Similarity	NPC259347
0.5882	Remote Similarity	NPC112
0.5859	Remote Similarity	NPC476377
0.5859	Remote Similarity	NPC476383
0.5833	Remote Similarity	NPC470934
0.5714	Remote Similarity	NPC472350
0.5714	Remote Similarity	NPC197316
0.5714	Remote Similarity	NPC89105
0.5648	Remote Similarity	NPC476378
0.5429	Remote Similarity	NPC600370
0.5385	Remote Similarity	NPC269141
0.5385	Remote Similarity	NPC470927
0.5385	Remote Similarity	NPC257970
0.5321	Remote Similarity	NPC476375
0.53	Remote Similarity	NPC483706
0.5248	Remote Similarity	NPC483705
0.5116	Remote Similarity	NPC213552
0.5048	Remote Similarity	NPC106677
0.5048	Remote Similarity	NPC47471
0.5046	Remote Similarity	NPC96795
0.5046	Remote Similarity	NPC264632

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476382 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4445
0.1-0.2	4574
0.2-0.3	128
0.3-0.4	2
0.4-0.5	0
0.5-0.6	1
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
0.5714	Remote Similarity	NPD7266	Phase 2

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