NPASS Compound

Natural Product: NPC473545

Natural Product ID	NPC473545
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Caseamembrin M
IUPAC Name	[(1R,3S,5S,6aR,7S,8S,10R,10aR)-1,3-diacetyloxy-10-butanoyloxy-7,8-dimethyl-7-(3-methylidenepent-4-enyl)-1,3,5,6,6a,8,9,10-octahydrobenzo[d][2]benzofuran-5-yl] 2-methylbutanoate
Synonyms	caseamembrin M
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL445213
PubChem CID	6326338
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0001757] Colensane and clerodane diterpenoids

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 90 92 0 0 0 0 0 0 0 0999 V2000 -5.6033 -4.4976 -0.2336 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6247 -3.3333 -0.0530 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9034 -3.5677 1.2335 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9122 -2.4970 1.5352 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1943 -2.5334 2.5648 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7196 -1.4024 0.7084 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7949 -0.4098 0.9947 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3668 0.9625 1.2083 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2354 1.7767 1.8345 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8451 2.8679 2.6136 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0915 1.9890 0.9520 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3776 0.5843 0.4552 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6775 -0.2874 -0.0234 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3305 -0.0276 -1.3442 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4815 -0.1690 -2.4610 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6278 0.7189 -3.5099 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4773 1.6435 -3.5243 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2461 0.6291 -4.7334 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1413 -1.2149 -1.3872 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1242 -2.1626 -1.3743 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1381 -1.6588 -0.3555 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9245 -2.1194 0.2169 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7164 -1.4160 1.2181 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2153 -0.0249 1.5154 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0921 -1.3067 0.8605 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1279 -1.8827 1.5514 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8588 -2.5527 2.5699 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5048 -1.6644 1.0325 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8204 -0.1849 0.9844 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1907 0.1003 0.4692 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4945 -2.4189 1.8847 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6405 -2.2903 -2.6581 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6273 -3.4032 -3.4487 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1194 -4.4488 -2.9411 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0674 -3.4079 -4.8398 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0415 2.4880 1.9065 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0921 2.9284 -0.1676 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2655 4.3586 -0.1320 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4440 5.0523 0.3594 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3555 5.8890 1.4359 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7657 4.9601 -0.2137 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0240 4.2208 -1.2589 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0977 -5.4414 0.0470 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3856 -4.3304 0.5582 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0797 -4.4943 -1.2135 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2464 -2.4004 0.0757 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9733 -3.2108 -0.9214 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4409 -4.5718 1.2153 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6282 -3.5669 2.0689 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2912 -0.6830 1.9570 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1565 0.9016 1.9791 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7324 1.4933 0.3492 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8834 1.0344 2.6732 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7511 3.3184 2.1439 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1416 3.5795 3.0509 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3164 2.3852 3.5509 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0921 0.8640 -0.3837 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0337 0.8140 -1.3994 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0836 -0.0531 -4.5840 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4354 0.3360 -5.5643 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5490 1.6831 -4.9609 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5335 -3.1341 -1.0093 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2649 -3.1251 -0.0710 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7299 -2.0609 2.1371 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7594 -0.0868 2.5244 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1159 0.6481 1.6642 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5537 -2.0566 0.0069 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7721 0.2205 2.0373 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0436 0.3722 0.4239 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3052 -0.0061 -0.6129 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9266 -0.4993 1.0563 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4158 1.1784 0.7124 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0391 -3.2882 2.3977 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9415 -1.7922 2.6755 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3352 -2.8064 1.2759 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8357 -3.1711 -5.5897 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3991 -4.3724 -5.0961 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7079 -2.6270 -4.9032 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6814 3.5008 2.2630 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9982 2.5484 1.4127 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1026 1.8881 2.8166 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6008 2.5228 -1.0949 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0343 2.8110 -0.5684 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2105 4.7255 -1.2365 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6849 4.9071 0.2373 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3847 5.9842 1.8671 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2293 6.4057 1.7897 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6089 5.5369 0.2455 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3802 3.6094 -1.8311 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0793 4.2222 -1.6178 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 2 0 4 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 9 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 2 0 16 18 1 0 14 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 23 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 1 0 29 30 1 0 28 31 1 0 20 32 1 0 32 33 1 0 33 34 2 0 33 35 1 0 11 36 1 1 11 37 1 0 37 38 1 0 38 39 1 0 39 40 2 0 39 41 1 0 41 42 2 0 13 7 1 0 24 12 1 0 13 21 1 6 1 43 1 0 1 44 1 0 1 45 1 0 2 46 1 0 2 47 1 0 3 48 1 0 3 49 1 0 7 50 1 1 8 51 1 0 8 52 1 0 9 53 1 1 10 54 1 0 10 55 1 0 10 56 1 0 12 57 1 6 14 58 1 1 18 59 1 0 18 60 1 0 18 61 1 0 20 62 1 1 22 63 1 0 23 64 1 1 24 65 1 0 24 66 1 0 28 67 1 0 29 68 1 0 29 69 1 0 30 70 1 0 30 71 1 0 30 72 1 0 31 73 1 0 31 74 1 0 31 75 1 0 35 76 1 0 35 77 1 0 35 78 1 0 36 79 1 0 36 80 1 0 36 81 1 0 37 82 1 0 37 83 1 0 38 84 1 0 38 85 1 0 40 86 1 0 40 87 1 0 41 88 1 0 42 89 1 0 42 90 1 0 M END

Standard InCHIKey	AELPJSZDZHHLQC-JUVNTAARSA-N
Standard InCHI	InChI=1S/C33H48O9/c1-10-13-28(36)41-27-16-21(6)32(9,15-14-19(4)11-2)26-18-24(40-29(37)20(5)12-3)17-25-30(38-22(7)34)42-31(33(25,26)27)39-23(8)35/h11,17,20-21,24,26-27,30-31H,2,4,10,12-16,18H2,1,3,5-9H3/t20?,21-,24+,26+,27+,30+,31-,32-,33-/m0/s1
SMILES	CCCC(=O)O[C@@H]1C[C@H](C)[C@]([C@@H]2[C@@]31[C@@H](OC(=O)C)O[C@H](C3=C[C@H](C2)OC(=O)C(CC)C)OC(=O)C)(C)CCC(=C)C=C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	588.33	Volume:	614.311 ? Van der Waals volume.
Dense:	0.958	LogP:	4.395 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.704 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.223 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	Rigid Bonds:	21.0
TPSA:	114.43 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.118	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.827	Fsp³:	0.697
MCE-18:	94.0 ? 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:	0.801	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.019 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.005 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.372	Promiscuous compounds:	0.511

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.919	MDCK Permeability:	-4.674
Pgp-inhibitor:	0.717	Pgp-substrate:	0.191
PAMPA:	0.04 ? 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):	0.0
20% Bioavailability (F20%):	0.975	30% Bioavailability (F30%):	0.936
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.999	MRP1:	0.999
Plasma Protein Binding (PPB):	97.117%	Volume Distribution (VD):	-0.125
Fu:	4.122% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.91
OATP1B3 inhibitor:	0.898	BCRP inhibitor:	0.353
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.993
CYP2C19-inhibitor:	0.036	CYP2C19-substrate:	0.412
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.009
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.721
CYP3A4-inhibitor:	0.007	CYP3A4-substrate:	0.613
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

8.263

Half-life (T1/2):

0.541

ADMET: Toxicity

hERG Blockers:	0.086	hERG Blockers (10um):	0.337
Human Hepatotoxicity (H-HT):	0.611	Drug-induced Liver Injury (DILI):	0.977
AMES Toxicity:	0.976	Rat Oral Acute Toxicity:	0.842
Maximum Recommended Daily Dose:	0.983	Skin Sensitization:	1.0
Carcinogencity:	0.75	Eye Corrosion:	0.0
Eye Irritation:	0.004	Respiratory Toxicity:	0.431
Drug-induced Neurotoxicity:	0.957	Ototoxicity:	0.628
Hematotoxicity:	0.851	Drug-induced Nephrotoxicity:	0.983
Genotoxicity:	0.991	RPMI-8226 Immunitoxicity:	0.378
A549 Cytotoxicity:	0.937	Hek293 Cytotoxicity:	0.616
BCF:	0.774 ? 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:	3.774 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.587 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.089 ? 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
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	n.a.	leaf	n.a.	PMID[14709876]
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	n.a.	twig	n.a.	PMID[14709876]
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	Leaves; Twigs	n.a.	n.a.	PMID[15043402]
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16309320]
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24498	Casearia membranacea	Species	Salicaceae	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
ED50	3

Activity Type	# Activity
Cell line	2
Non-molecular	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
NPT579	Cell line	DLD-1	Homo sapiens	ED50	=	14.2	ug ml-1	PubChem BioAssay data set
NPT91	Cell line	KB	Homo sapiens	ED50	=	18.4	ug ml-1	PubChem BioAssay data set
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	14.4	ug ml-1	PMID[16309320]

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 NPC473545 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	24099
0.1-0.2	23856
0.2-0.3	1762
0.3-0.4	25
0.4-0.5	46
0.5-0.6	28
0.6-0.7	23
0.7-0.8	0
0.8-0.85	2
0.85-0.9	4
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9153	High Similarity	NPC488236
0.873	High Similarity	NPC472187
0.8689	High Similarity	NPC471366
0.8689	High Similarity	NPC476800
0.8689	High Similarity	NPC488237
0.8361	Intermediate Similarity	NPC481019
0.8226	Intermediate Similarity	NPC472188
0.7937	Intermediate Similarity	NPC472186
0.7903	Intermediate Similarity	NPC481020
0.7812	Intermediate Similarity	NPC488649
0.7742	Intermediate Similarity	NPC171598
0.7692	Intermediate Similarity	NPC481017
0.75	Intermediate Similarity	NPC318917
0.7463	Intermediate Similarity	NPC488963
0.7302	Intermediate Similarity	NPC472189
0.7231	Intermediate Similarity	NPC488235
0.7188	Intermediate Similarity	NPC481018
0.7015	Intermediate Similarity	NPC473204
0.697	Remote Similarity	NPC471362
0.697	Remote Similarity	NPC471372
0.6714	Remote Similarity	NPC48548
0.6709	Remote Similarity	NPC488962
0.6618	Remote Similarity	NPC479937
0.6471	Remote Similarity	NPC479935
0.6438	Remote Similarity	NPC127933
0.6389	Remote Similarity	NPC488219
0.6364	Remote Similarity	NPC603601
0.6338	Remote Similarity	NPC475889
0.6338	Remote Similarity	NPC7613
0.6338	Remote Similarity	NPC479942
0.6301	Remote Similarity	NPC488221
0.6301	Remote Similarity	NPC488220
0.6301	Remote Similarity	NPC488216
0.6197	Remote Similarity	NPC7644
0.6176	Remote Similarity	NPC606965
0.6111	Remote Similarity	NPC88013
0.6087	Remote Similarity	NPC600724
0.6081	Remote Similarity	NPC125423
0.6026	Remote Similarity	NPC473216
0.6	Remote Similarity	NPC479939
0.6	Remote Similarity	NPC40728
0.5974	Remote Similarity	NPC486752
0.5972	Remote Similarity	NPC471365
0.589	Remote Similarity	NPC217921
0.589	Remote Similarity	NPC238397
0.589	Remote Similarity	NPC135015
0.5857	Remote Similarity	NPC132395
0.5857	Remote Similarity	NPC479934
0.5857	Remote Similarity	NPC471364
0.5775	Remote Similarity	NPC479936
0.5733	Remote Similarity	NPC471363
0.5694	Remote Similarity	NPC479943
0.5625	Remote Similarity	NPC473399
0.5541	Remote Similarity	NPC479940
0.5417	Remote Similarity	NPC488651
0.5417	Remote Similarity	NPC488648
0.5405	Remote Similarity	NPC479938
0.5342	Remote Similarity	NPC88507
0.5301	Remote Similarity	NPC486759
0.5301	Remote Similarity	NPC488217
0.5301	Remote Similarity	NPC488218
0.5195	Remote Similarity	NPC479941
0.5181	Remote Similarity	NPC162569
0.5181	Remote Similarity	NPC35160
0.5132	Remote Similarity	NPC128795
0.5065	Remote Similarity	NPC330003
0.5065	Remote Similarity	NPC470321
0.5065	Remote Similarity	NPC264867
0.5065	Remote Similarity	NPC473207

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473545 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7723
0.1-0.2	1406
0.2-0.3	21
0.3-0.4	0
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