NPASS Compound

Natural Product: NPC34390

Natural Product ID	NPC34390
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Periplocymarin
IUPAC Name	3-[(3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-3-[(2R,4R,5R,6R)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-10,13-dimethyl-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2H-furan-5-one
Synonyms	periplocymarin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL502236
PubChem CID	44566918
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides 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 84 89 0 0 0 0 0 0 0 0999 V2000 8.0283 1.6294 2.1547 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5175 1.0990 0.9711 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2165 1.5321 0.7316 C 0 0 2 0 0 0 0 0 0 0 0 0 5.2509 0.3921 0.6669 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3805 0.3955 -0.5798 C 0 0 2 0 0 0 0 0 0 0 0 0 3.7868 -0.8620 -0.6148 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4162 -0.8392 -0.6097 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7796 -1.4470 -1.8333 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3072 -1.1343 -1.7420 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3574 -1.7302 -0.5309 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4306 -1.6492 0.7295 C 0 0 2 0 0 0 0 0 0 0 0 0 1.9195 -1.6053 0.5674 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2055 -2.7721 1.5687 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0176 -0.3901 1.4576 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4213 -0.3649 1.8829 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2970 -1.2138 0.9519 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7118 -1.0149 -0.4166 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6809 -1.6055 -1.4147 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8965 -0.7036 -1.4156 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4649 -0.4342 -0.0845 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7369 -1.0026 1.0960 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3798 -2.2384 1.3713 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1324 -0.0945 2.2391 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7394 1.1623 1.6621 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5074 1.0775 0.1674 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.5960 1.7500 -0.5813 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5889 2.4486 -0.0684 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4585 2.9530 -1.1237 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5102 3.6635 -0.9861 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9160 2.5079 -2.3070 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7671 1.7577 -2.0677 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9127 -0.8917 -0.0689 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5989 -3.1972 -0.8379 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2287 0.4382 -1.6787 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1370 1.4483 -1.7042 C 0 0 1 0 0 0 0 0 0 0 0 0 6.1300 2.3683 -0.5129 C 0 0 1 0 0 0 0 0 0 0 0 0 4.9734 3.1137 -0.4686 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5278 0.7957 -1.7192 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4339 1.3453 3.0464 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0557 1.2530 2.3350 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1098 2.7340 2.1154 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9360 2.2029 1.5818 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6086 0.3477 1.5912 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8530 -0.5535 0.7169 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6560 1.2136 -0.5533 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0952 0.2259 -0.5776 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1430 -1.0017 -2.7818 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8756 -2.5525 -1.8546 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2520 -1.4773 -2.6370 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2238 -0.0198 -1.6556 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3575 -1.2603 1.5279 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2786 -2.6697 0.4456 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5244 -2.4786 2.4620 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6885 -0.2536 2.3368 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2518 0.4606 0.7701 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7237 0.7203 1.8270 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4714 -0.7558 2.9113 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0379 -2.2766 1.2393 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5714 0.0507 -0.6766 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0082 -2.6185 -1.1789 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2808 -1.5731 -2.4632 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5988 0.2143 -1.9632 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6287 -1.2295 -2.1023 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6757 -2.6808 0.5476 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9240 -0.5455 2.8981 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3039 0.1242 2.9428 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3094 2.0877 2.0363 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8339 1.1901 1.8621 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5513 1.5372 -0.1222 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7903 2.6617 0.9673 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8694 0.7551 -2.4961 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8996 2.3131 -2.4930 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6183 -0.1238 -0.3782 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0465 -1.7598 -0.7770 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1559 -1.3275 0.9392 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3077 -3.7773 -0.5507 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4497 -3.5444 -0.2425 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7196 -3.3614 -1.9340 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9941 2.0353 -2.6360 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0451 3.0135 -0.5100 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1010 4.0450 -0.8297 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7748 0.5337 -2.7623 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2801 1.5184 -1.3509 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5464 -0.0847 -1.0489 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 11 13 1 1 11 14 1 0 14 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 1 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 28 30 1 0 30 31 1 0 20 32 1 6 10 33 1 6 5 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 35 38 1 0 36 3 1 0 12 7 1 0 21 16 1 0 31 26 1 0 17 10 1 0 25 20 1 0 1 39 1 0 1 40 1 0 1 41 1 0 3 42 1 1 4 43 1 0 4 44 1 0 5 45 1 1 7 46 1 1 8 47 1 0 8 48 1 0 9 49 1 0 9 50 1 0 12 51 1 0 12 52 1 0 13 53 1 0 14 54 1 0 14 55 1 0 15 56 1 0 15 57 1 0 16 58 1 1 17 59 1 6 18 60 1 0 18 61 1 0 19 62 1 0 19 63 1 0 22 64 1 0 23 65 1 0 23 66 1 0 24 67 1 0 24 68 1 0 25 69 1 1 27 70 1 0 31 71 1 0 31 72 1 0 32 73 1 0 32 74 1 0 32 75 1 0 33 76 1 0 33 77 1 0 33 78 1 0 35 79 1 6 36 80 1 6 37 81 1 0 38 82 1 0 38 83 1 0 38 84 1 0 M END

Standard InCHIKey	XRWQBDJPMXRDOQ-ZVXDPGNRSA-N
Standard InCHI	InChI=1S/C30H46O8/c1-17-26(32)23(35-4)14-25(37-17)38-19-5-9-27(2)21-6-10-28(3)20(18-13-24(31)36-16-18)8-12-30(28,34)22(21)7-11-29(27,33)15-19/h13,17,19-23,25-26,32-34H,5-12,14-16H2,1-4H3/t17-,19+,20-,21+,22-,23-,25+,26-,27-,28-,29+,30+/m1/s1
SMILES	CO[C@@H]1C[C@H](O[C@H]2CC[C@]3([C@](C2)(O)CC[C@@H]2[C@@H]3CC[C@]3([C@]2(O)CC[C@@H]3C2=CC(=O)OC2)C)C)O[C@@H]([C@H]1O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	534.32	Volume:	541.146 ? Van der Waals volume.
Dense:	0.987	LogP:	1.646 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.12 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.681 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	32.0
TPSA:	114.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	3.0	Rings:	6.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.372	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.196	Fsp³:	0.9
MCE-18:	112.281 ? 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:	0.795	Fluc inhibitor:	0.002 ? 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:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.176	Promiscuous compounds:	0.407

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.499	MDCK Permeability:	-5.146
Pgp-inhibitor:	0.01	Pgp-substrate:	0.984
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):	0.011
20% Bioavailability (F20%):	0.433	30% Bioavailability (F30%):	0.129
50% Bioavailability (F50%):	0.943

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.308	MRP1:	0.931
Plasma Protein Binding (PPB):	85.645%	Volume Distribution (VD):	-0.106
Fu:	13.479% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.199
BSEP inhibitor:	0.463

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.991	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.038	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.124
CYP2B6-substrate:	0.002	CYP2C8-inhibitor:	0.172
HLM stability:	0.847 ? 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):

5.755

Half-life (T1/2):

2.956

ADMET: Toxicity

hERG Blockers:	0.297	hERG Blockers (10um):	0.85
Human Hepatotoxicity (H-HT):	0.779	Drug-induced Liver Injury (DILI):	0.837
AMES Toxicity:	0.852	Rat Oral Acute Toxicity:	0.992
Maximum Recommended Daily Dose:	1.0	Skin Sensitization:	1.0
Carcinogencity:	0.959	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.996
Drug-induced Neurotoxicity:	0.022	Ototoxicity:	0.589
Hematotoxicity:	0.317	Drug-induced Nephrotoxicity:	0.966
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.813
A549 Cytotoxicity:	0.923	Hek293 Cytotoxicity:	0.995
BCF:	0.595 ? 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:	3.257 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.667 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.056 ? 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
NPO4040	Kunzea ericifolia	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10543906]
NPO32958	Streptocaulon juventas	Species	Apocynaceae	Eukaryota	n.a.	Vietnamese	n.a.	PMID[14640513]
NPO12796	Periploca sepium	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28294615]
NPO32958	Streptocaulon juventas	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31120251]
NPO12796	Periploca sepium	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12796	Periploca sepium	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12796	Periploca sepium	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12796	Periploca sepium	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12796	Periploca sepium	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO3290	Agathosma puberula	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12796	Periploca sepium	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO813	Streptomyces longisporus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO4040	Kunzea ericifolia	Species	Myrtaceae	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	1

Activity Type	# Activity
Cell line	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
NPT453	Cell line	HT-1080	Homo sapiens	IC50	=	96.0	nM	PMID[14640513]

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 NPC34390 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	14019
0.1-0.2	32211
0.2-0.3	3323
0.3-0.4	94
0.4-0.5	108
0.5-0.6	58
0.6-0.7	27
0.7-0.8	1
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
0.8667	High Similarity	NPC180079
0.7763	Intermediate Similarity	NPC474418
0.7595	Intermediate Similarity	NPC84949
0.7595	Intermediate Similarity	NPC480562
0.7595	Intermediate Similarity	NPC74945
0.7595	Intermediate Similarity	NPC31354
0.7595	Intermediate Similarity	NPC69576
0.7407	Intermediate Similarity	NPC483822
0.7222	Intermediate Similarity	NPC329636
0.7215	Intermediate Similarity	NPC99728
0.7215	Intermediate Similarity	NPC87250
0.7215	Intermediate Similarity	NPC244402
0.7215	Intermediate Similarity	NPC50305
0.7073	Intermediate Similarity	NPC484212
0.6914	Remote Similarity	NPC84987
0.6875	Remote Similarity	NPC158344
0.6829	Remote Similarity	NPC6108
0.6829	Remote Similarity	NPC89514
0.6629	Remote Similarity	NPC475629
0.6517	Remote Similarity	NPC475556
0.6517	Remote Similarity	NPC311706
0.6353	Remote Similarity	NPC10823
0.6237	Remote Similarity	NPC146857
0.6235	Remote Similarity	NPC157376
0.6235	Remote Similarity	NPC17896
0.6235	Remote Similarity	NPC469755
0.6235	Remote Similarity	NPC284406
0.6235	Remote Similarity	NPC99080
0.6235	Remote Similarity	NPC197707
0.6235	Remote Similarity	NPC251866
0.6235	Remote Similarity	NPC142066
0.6235	Remote Similarity	NPC603972
0.6207	Remote Similarity	NPC484202
0.6163	Remote Similarity	NPC152615
0.6092	Remote Similarity	NPC77319
0.6092	Remote Similarity	NPC471351
0.6092	Remote Similarity	NPC471355
0.6	Remote Similarity	NPC103534
0.6	Remote Similarity	NPC44899
0.6	Remote Similarity	NPC304260
0.6	Remote Similarity	NPC29639
0.593	Remote Similarity	NPC219085
0.5921	Remote Similarity	NPC97487
0.5843	Remote Similarity	NPC93883
0.5814	Remote Similarity	NPC471633
0.58	Remote Similarity	NPC329675
0.58	Remote Similarity	NPC194716
0.5795	Remote Similarity	NPC199428
0.5795	Remote Similarity	NPC109448
0.5795	Remote Similarity	NPC310341
0.5789	Remote Similarity	NPC469749
0.573	Remote Similarity	NPC250556
0.5696	Remote Similarity	NPC72772
0.5667	Remote Similarity	NPC305574
0.5638	Remote Similarity	NPC608063
0.5567	Remote Similarity	NPC247190
0.5521	Remote Similarity	NPC55532
0.5506	Remote Similarity	NPC477580
0.5474	Remote Similarity	NPC32793
0.5474	Remote Similarity	NPC116075
0.5455	Remote Similarity	NPC99620
0.5435	Remote Similarity	NPC469753
0.5408	Remote Similarity	NPC329986
0.5408	Remote Similarity	NPC140092
0.5393	Remote Similarity	NPC484211
0.5393	Remote Similarity	NPC486129
0.5376	Remote Similarity	NPC72260
0.5375	Remote Similarity	NPC10232
0.5333	Remote Similarity	NPC486126
0.5333	Remote Similarity	NPC469750
0.5326	Remote Similarity	NPC9499
0.5326	Remote Similarity	NPC471360
0.5326	Remote Similarity	NPC469751
0.5326	Remote Similarity	NPC471361
0.5326	Remote Similarity	NPC86159
0.5326	Remote Similarity	NPC469752
0.5326	Remote Similarity	NPC469754
0.5326	Remote Similarity	NPC70542
0.5312	Remote Similarity	NPC603096
0.5281	Remote Similarity	NPC473852
0.5275	Remote Similarity	NPC76572
0.5275	Remote Similarity	NPC193382
0.5269	Remote Similarity	NPC471354
0.5269	Remote Similarity	NPC27507
0.5222	Remote Similarity	NPC309034
0.5165	Remote Similarity	NPC5311
0.5165	Remote Similarity	NPC77299
0.5165	Remote Similarity	NPC480906
0.5161	Remote Similarity	NPC471359
0.5109	Remote Similarity	NPC480914
0.5096	Remote Similarity	NPC475419
0.5055	Remote Similarity	NPC203862
0.5054	Remote Similarity	NPC88668
0.5054	Remote Similarity	NPC290693
0.5051	Remote Similarity	NPC486143
0.5051	Remote Similarity	NPC486135
0.5051	Remote Similarity	NPC486142
0.5051	Remote Similarity	NPC486137
0.5051	Remote Similarity	NPC486149

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC34390 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5787
0.1-0.2	3250
0.2-0.3	99
0.3-0.4	1
0.4-0.5	6
0.5-0.6	4
0.6-0.7	2
0.7-0.8	1
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
0.7195	Intermediate Similarity	NPD7516	Pre-clinical
0.6235	Remote Similarity	NPD7319	Approved
0.6196	Remote Similarity	NPD8377	Phase 4
0.573	Remote Similarity	NPD7507	Pre-clinical
0.5376	Remote Similarity	NPD8294	Phase 4
0.5306	Remote Similarity	NPD8378	Pre-clinical
0.5306	Remote Similarity	NPD8379	Approved

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