NPASS Compound

Natural Product: NPC99957

Natural Product ID	NPC99957
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-Hydroxy-6-Methoxy-2-Methylchromone-7-O-Rutinoside
IUPAC Name	5-hydroxy-6-methoxy-2-methyl-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-2-yl]oxychromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL564024
PubChem CID	44139362
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002105] Glycosyl compounds [CHEMONTID:0004165] Phenolic 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 67 70 0 0 0 0 0 0 0 0999 V2000 5.0588 4.4602 -0.3192 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0285 3.2131 0.5162 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0275 3.0024 1.4208 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0181 1.8518 2.2056 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9229 1.6334 3.0439 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9708 0.9841 2.0068 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9858 1.2368 1.0840 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9358 0.3306 0.9094 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8256 -0.8339 1.6273 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8468 -1.0776 2.5714 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8682 -0.1800 2.7301 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8718 -0.4314 3.6661 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8401 -2.2219 3.3540 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5006 -3.4000 2.8754 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8249 -1.7627 1.5058 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7632 -1.6557 0.6246 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7058 -2.8456 -0.2900 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6462 -3.1332 -0.8544 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7862 -2.6404 -0.0343 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4224 -1.2340 0.4489 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5771 -0.5479 1.0964 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6206 -0.2184 0.2503 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3030 0.6537 -0.7641 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5186 0.1396 -2.1487 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0889 1.2587 -2.9940 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4749 1.5428 -2.4405 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2871 1.8361 -0.9523 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.8788 3.1973 -0.7050 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9367 1.8914 -0.6210 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2721 0.4018 -2.5229 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2989 2.3967 -2.7356 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3869 -0.4202 -2.7343 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3960 -1.5071 1.3894 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9660 -2.7014 -0.7207 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8207 -4.5259 -1.0250 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6358 -2.6432 -1.3101 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0650 2.3366 0.3871 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7616 4.3246 -1.1495 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3834 5.3355 0.2908 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0553 4.6813 -0.7400 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8092 3.7314 1.5129 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2131 0.6021 0.1734 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7588 -0.8327 3.3972 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2165 -3.7932 3.6448 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7247 -4.1217 2.6107 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0629 -3.1641 1.9316 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8420 -0.7261 0.0411 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0439 -3.7425 0.2695 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7355 -2.7002 -1.8726 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8722 -3.3324 0.8553 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9882 -0.7036 -0.3950 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1811 0.4400 1.4781 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9591 -1.0715 1.9862 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2040 0.8962 -0.6644 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2981 -0.6773 -2.1740 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0984 1.0231 -4.0669 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9738 2.3649 -2.9722 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7633 1.0803 -0.3146 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2874 3.3087 0.3182 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6539 3.4449 -1.4888 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0763 3.9471 -0.8588 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7341 0.3344 -3.3881 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8156 3.2288 -2.7777 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7227 -0.8762 -3.5689 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7214 -3.0796 -0.2253 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2834 -5.0205 -0.3338 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4821 -3.2879 -2.0606 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 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 10 13 1 0 13 14 1 0 9 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 27 29 1 0 26 30 1 0 25 31 1 0 24 32 1 0 20 33 1 0 19 34 1 0 18 35 1 0 17 36 1 0 7 37 1 0 37 2 1 0 11 6 1 0 33 16 1 0 29 23 1 0 1 38 1 0 1 39 1 0 1 40 1 0 3 41 1 0 8 42 1 0 12 43 1 0 14 44 1 0 14 45 1 0 14 46 1 0 16 47 1 6 17 48 1 1 18 49 1 6 19 50 1 1 20 51 1 6 21 52 1 0 21 53 1 0 23 54 1 6 24 55 1 1 25 56 1 6 26 57 1 6 27 58 1 1 28 59 1 0 28 60 1 0 28 61 1 0 30 62 1 0 31 63 1 0 32 64 1 0 34 65 1 0 35 66 1 0 36 67 1 0 M END

Standard InCHIKey	SBMOEJYIIKODKJ-JVBHFNPYSA-N
Standard InCHI	InChI=1S/C23H30O14/c1-7-4-9(24)13-10(34-7)5-11(21(32-3)16(13)27)36-23-20(31)18(29)15(26)12(37-23)6-33-22-19(30)17(28)14(25)8(2)35-22/h4-5,8,12,14-15,17-20,22-23,25-31H,6H2,1-3H3/t8-,12+,14-,15+,17+,18-,19+,20+,22+,23+/m0/s1
SMILES	Cc1cc(=O)c2c(cc(c(c2O)OC)O[C@H]2[C@@H]([C@H]([C@@H]([C@@H](CO[C@H]3[C@@H]([C@@H]([C@H]([C@H](C)O3)O)O)O)O2)O)O)O)o1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	530.16	Volume:	482.019 ? Van der Waals volume.
Dense:	1.1	LogP:	-0.71 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.487 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.095 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	24.0
TPSA:	217.97 ? 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:	0.212	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.682	Fsp³:	0.609
MCE-18:	102.676 ? 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:	0.542	Fluc inhibitor:	0.036 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.167 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.239 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.036	Promiscuous compounds:	0.216

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.223	MDCK Permeability:	-5.317
Pgp-inhibitor:	0.002	Pgp-substrate:	0.803
PAMPA:	0.995 ? 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):	0.067
20% Bioavailability (F20%):	0.064	30% Bioavailability (F30%):	0.706
50% Bioavailability (F50%):	0.947

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.876
Plasma Protein Binding (PPB):	76.16%	Volume Distribution (VD):	-0.318
Fu:	23.676% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.003
BSEP inhibitor:	0.07

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:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.058
HLM stability:	0.004 ? 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):

1.391

Half-life (T1/2):

3.923

ADMET: Toxicity

hERG Blockers:	0.02	hERG Blockers (10um):	0.151
Human Hepatotoxicity (H-HT):	0.38	Drug-induced Liver Injury (DILI):	0.76
AMES Toxicity:	0.862	Rat Oral Acute Toxicity:	0.014
Maximum Recommended Daily Dose:	0.022	Skin Sensitization:	0.932
Carcinogencity:	0.043	Eye Corrosion:	0.0
Eye Irritation:	0.142	Respiratory Toxicity:	0.006
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.939
Hematotoxicity:	0.169	Drug-induced Nephrotoxicity:	0.439
Genotoxicity:	0.366	RPMI-8226 Immunitoxicity:	0.194
A549 Cytotoxicity:	0.143	Hek293 Cytotoxicity:	0.211
BCF:	0.148 ? 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:	2.738 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.267 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.425 ? 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
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	twig	n.a.	DOI[10.1021/np8006342]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	fruit	n.a.	DOI[10.1021/np8006342]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1021/np8006342]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	flower	n.a.	DOI[10.1021/np8006342]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	fruit	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	leaf	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	flower	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	twig	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	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
GI50	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
NPT81	Cell line	A549	Homo sapiens	GI50	=	400.0	nM	PMID[19405508]
NPT139	Cell line	HT-29	Homo sapiens	GI50	=	6000.0	nM	PMID[19405508]
NPT83	Cell line	MCF7	Homo sapiens	GI50	=	800.0	nM	PMID[19405508]

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 NPC99957 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	16496
0.1-0.2	28867
0.2-0.3	3636
0.3-0.4	646
0.4-0.5	156
0.5-0.6	52
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	Natural Product ID
0.7595	Intermediate Similarity	NPC181616
0.6897	Remote Similarity	NPC204693
0.5978	Remote Similarity	NPC213052
0.5833	Remote Similarity	NPC114740
0.5625	Remote Similarity	NPC483707
0.5604	Remote Similarity	NPC211594
0.557	Remote Similarity	NPC469622
0.5532	Remote Similarity	NPC22062
0.5532	Remote Similarity	NPC473634
0.5532	Remote Similarity	NPC138811
0.551	Remote Similarity	NPC473073
0.5474	Remote Similarity	NPC473571
0.5474	Remote Similarity	NPC110941
0.5426	Remote Similarity	NPC44931
0.5417	Remote Similarity	NPC126784
0.5417	Remote Similarity	NPC241423
0.5368	Remote Similarity	NPC210073
0.5366	Remote Similarity	NPC479450
0.5361	Remote Similarity	NPC470443
0.5352	Remote Similarity	NPC30647
0.5306	Remote Similarity	NPC209296
0.5269	Remote Similarity	NPC172807
0.5263	Remote Similarity	NPC67105
0.5253	Remote Similarity	NPC294722
0.5213	Remote Similarity	NPC254540
0.5208	Remote Similarity	NPC233994
0.5208	Remote Similarity	NPC475155
0.5208	Remote Similarity	NPC303913
0.5158	Remote Similarity	NPC187379
0.5155	Remote Similarity	NPC186816
0.5152	Remote Similarity	NPC257714
0.5119	Remote Similarity	NPC191154
0.5104	Remote Similarity	NPC173582
0.5104	Remote Similarity	NPC265885
0.5104	Remote Similarity	NPC181465
0.5104	Remote Similarity	NPC215710
0.5104	Remote Similarity	NPC473438
0.5104	Remote Similarity	NPC227508
0.5104	Remote Similarity	NPC253788
0.5102	Remote Similarity	NPC475366
0.5052	Remote Similarity	NPC203259
0.5052	Remote Similarity	NPC65563
0.5052	Remote Similarity	NPC33054
0.5052	Remote Similarity	NPC470949
0.5052	Remote Similarity	NPC84494
0.5052	Remote Similarity	NPC176740
0.5052	Remote Similarity	NPC471725
0.5052	Remote Similarity	NPC134532
0.5052	Remote Similarity	NPC602582
0.5051	Remote Similarity	NPC211532
0.5051	Remote Similarity	NPC488364
0.505	Remote Similarity	NPC476472
0.505	Remote Similarity	NPC294815
0.505	Remote Similarity	NPC16194

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC99957 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4096
0.1-0.2	4974
0.2-0.3	69
0.3-0.4	5
0.4-0.5	4
0.5-0.6	2
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
0.5306	Remote Similarity	NPD7054	Phase 4
0.5052	Remote Similarity	NPD6797	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