NPASS Compound

Natural Product: NPC262858

Natural Product ID	NPC262858
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3Alpha-Hydroxymasticadienonic Acid
IUPAC Name	(Z,6S)-6-[(3R,5R,9R,10R,13S,14S,17S)-3-hydroxy-4,4,10,13,14-pentamethyl-2,3,5,6,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methylhept-2-enoic acid
Synonyms	3Alpha-Hydroxymasticadienonic Acid
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2036658
PubChem CID	70692334
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

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 81 84 0 0 0 0 0 0 0 0999 V2000 2.9885 2.0694 1.1056 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2424 0.9755 0.0133 C 0 0 1 0 0 0 0 0 0 0 0 0 4.6189 0.5077 0.4204 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2754 -0.5518 -0.4016 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6235 -0.7686 0.2136 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7559 -0.5466 -0.3689 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0223 -0.8257 0.4074 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9097 -0.0331 -1.7008 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1120 0.1200 -2.1241 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9209 0.3134 -2.5718 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2423 -0.1032 0.1705 C 0 0 2 0 0 0 0 0 0 0 0 0 2.3329 -1.1546 -0.8686 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8976 -1.2559 -1.4845 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0999 -0.9615 -0.2847 C 0 0 2 0 0 0 0 0 0 0 0 0 0.2870 -2.1005 0.6864 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3150 -0.6828 -0.4127 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1075 -1.4729 -1.1207 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5604 -1.2707 -1.3078 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0959 -0.0541 -0.6480 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.5757 0.0112 -0.5622 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0971 -0.0494 -2.0030 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2346 -1.0608 0.2211 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9741 1.3566 -0.0280 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.3816 1.5503 1.3317 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8880 1.3889 1.3797 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3808 0.1487 0.6764 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4260 -1.0657 1.5395 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9459 0.5001 0.2516 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2184 0.9687 1.4461 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2166 0.5456 1.5461 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8092 0.3197 0.1888 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5136 1.4123 -0.7857 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5046 2.4037 -0.8399 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8786 2.7401 0.9932 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1109 2.6598 0.8896 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0766 1.5826 2.0700 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3380 1.4548 -0.9613 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5936 0.1614 1.4973 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3300 1.3891 0.4800 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7101 -1.5190 -0.1619 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2687 -0.4030 -1.4677 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6453 -1.1469 1.2419 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7976 -0.7157 1.4821 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4258 -1.8115 0.1311 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7593 -0.0690 0.1151 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0432 1.0863 -3.1969 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4791 -0.5367 1.2130 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0412 -0.9780 -1.6678 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5528 -2.1486 -0.4003 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8114 -2.3095 -1.8028 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7995 -0.6165 -2.3522 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5408 -2.2127 1.4100 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2558 -2.1482 1.1752 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2267 -3.0379 0.0529 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7077 -2.3714 -1.6364 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7205 -1.1582 -2.4169 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1228 -2.1856 -1.0238 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7796 0.8263 -1.2852 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3408 0.4229 -2.6953 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2699 -1.0788 -2.3331 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0012 0.5561 -2.0670 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4947 -0.7789 1.2706 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7215 -2.0312 0.2329 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2390 -1.2633 -0.2572 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0628 1.4909 0.0499 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8942 0.9668 2.1329 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5792 2.6281 1.6114 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4484 2.3130 0.9070 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5976 1.3752 2.4493 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3057 -1.0093 2.2210 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4295 -1.9997 0.9391 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5231 -1.1185 2.1782 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1375 1.3302 -0.4960 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2118 2.0984 1.4231 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6905 0.7117 2.4143 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2364 -0.4524 2.0767 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7292 1.2390 2.1987 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4043 1.8669 -1.2693 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0277 2.2974 -0.2760 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0961 1.0711 -1.6738 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7904 2.1989 -1.7499 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 2 0 6 7 1 0 6 8 1 0 8 9 2 0 8 10 1 0 2 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 1 14 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 20 22 1 0 20 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 1 26 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 6 23 33 1 0 31 11 1 0 31 14 1 0 28 16 1 0 26 19 1 0 1 34 1 0 1 35 1 0 1 36 1 0 2 37 1 6 3 38 1 0 3 39 1 0 4 40 1 0 4 41 1 0 5 42 1 0 7 43 1 0 7 44 1 0 7 45 1 0 10 46 1 0 11 47 1 1 12 48 1 0 12 49 1 0 13 50 1 0 13 51 1 0 15 52 1 0 15 53 1 0 15 54 1 0 17 55 1 0 18 56 1 0 18 57 1 0 19 58 1 6 21 59 1 0 21 60 1 0 21 61 1 0 22 62 1 0 22 63 1 0 22 64 1 0 23 65 1 1 24 66 1 0 24 67 1 0 25 68 1 0 25 69 1 0 27 70 1 0 27 71 1 0 27 72 1 0 28 73 1 6 29 74 1 0 29 75 1 0 30 76 1 0 30 77 1 0 32 78 1 0 32 79 1 0 32 80 1 0 33 81 1 0 M END

Standard InCHIKey	UILQHUKSFUOOLH-ABWNVCESSA-N
Standard InCHI	InChI=1S/C30H48O3/c1-19(9-8-10-20(2)26(32)33)21-13-17-30(7)23-11-12-24-27(3,4)25(31)15-16-28(24,5)22(23)14-18-29(21,30)6/h10-11,19,21-22,24-25,31H,8-9,12-18H2,1-7H3,(H,32,33)/b20-10-/t19-,21-,22-,24-,25+,28+,29-,30+/m0/s1
SMILES	C[C@@H](CC/C=C(/C)C(=O)O)[C@@H]1CC[C@]2(C)C3=CC[C@H]4C(C)(C)[C@@H](CC[C@]4(C)[C@H]3CC[C@@]12C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	456.36	Volume:	511.671 ? Van der Waals volume.
Dense:	0.892	LogP:	5.705 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.161 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.416 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	22.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.335	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.663	Fsp³:	0.833
MCE-18:	81.455 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.619	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.008 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.525	Promiscuous compounds:	0.2

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.998	MDCK Permeability:	-4.797
Pgp-inhibitor:	0.021	Pgp-substrate:	0.03
PAMPA:	0.992 ? 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):	0.003
20% Bioavailability (F20%):	0.934	30% Bioavailability (F30%):	0.456
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.048	MRP1:	0.987
Plasma Protein Binding (PPB):	90.729%	Volume Distribution (VD):	-0.461
Fu:	8.472% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.962	BCRP inhibitor:	0.171
BSEP inhibitor:	0.857

ADMET: Metabolism

CYP1A2-inhibitor:	0.013	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.99	CYP2C19-substrate:	0.791
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.003
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.01 ? 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):

5.274

Half-life (T1/2):

0.685

ADMET: Toxicity

hERG Blockers:	0.071	hERG Blockers (10um):	0.112
Human Hepatotoxicity (H-HT):	0.729	Drug-induced Liver Injury (DILI):	0.679
AMES Toxicity:	0.193	Rat Oral Acute Toxicity:	0.452
Maximum Recommended Daily Dose:	0.653	Skin Sensitization:	0.924
Carcinogencity:	0.565	Eye Corrosion:	0.009
Eye Irritation:	0.386	Respiratory Toxicity:	0.88
Drug-induced Neurotoxicity:	0.11	Ototoxicity:	0.724
Hematotoxicity:	0.668	Drug-induced Nephrotoxicity:	0.702
Genotoxicity:	0.71	RPMI-8226 Immunitoxicity:	0.038
A549 Cytotoxicity:	0.163	Hek293 Cytotoxicity:	0.247
BCF:	1.595 ? 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:	4.319 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.638 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.141 ? 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
NPO1486	Aphrocallistes beatrix	Species	Aphrocallistidae	Eukaryota	n.a.	n.a.	n.a.	PMID[19459694]
NPO8802	Cymbopogon nardus	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32304294]
NPO8802	Cymbopogon nardus	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[34946632]
NPO9100	Amsonia angustifolia	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8802	Cymbopogon nardus	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7854	Lepraria latebrarum	Species	Stereocaulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7244	Cylicodiscus gabunensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14716	Lilium speciosum	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8802	Cymbopogon nardus	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8802	Cymbopogon nardus	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7442	Dysoxylum pettigrewianum	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27627	Cylindropuntia fulgida	Species	Cactaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7854	Lepraria latebrarum	Species	Stereocaulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16450	Trametes suaveolens	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1486	Aphrocallistes beatrix	Species	Aphrocallistidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14716	Lilium speciosum	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7244	Cylicodiscus gabunensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9747	Pimpinella puberula	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8802	Cymbopogon nardus	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2447	Eriodictyon angustifolium	Species	Namaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9100	Amsonia angustifolia	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1713	Phytophthora megasperma	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8495	Saussurea controversa	Species	Asteraceae	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	3
Activity	5

Activity Type	# Activity
Cell line	3
Others	5

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
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	28900.0	nM	PMID[22458644]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	20100.0	nM	PMID[22458644]
NPT762	Cell line	A-431	Homo sapiens	IC50	=	40000.0	nM	PMID[22458644]
NPT2	Others	Unspecified	n.a.	Activity	=	20.0	%	PMID[22458644]
NPT2	Others	Unspecified	n.a.	Activity	=	50.0	%	PMID[22458644]
NPT2	Others	Unspecified	n.a.	Activity	=	25.0	%	PMID[22458644]
NPT2	Others	Unspecified	n.a.	Activity	=	20.0	nmol	PMID[22458644]

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 NPC262858 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	22344
0.1-0.2	22169
0.2-0.3	4216
0.3-0.4	832
0.4-0.5	234
0.5-0.6	46
0.6-0.7	14
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC472240
0.7015	Intermediate Similarity	NPC472239
0.7015	Intermediate Similarity	NPC480720
0.6618	Remote Similarity	NPC146554
0.6462	Remote Similarity	NPC30166
0.6418	Remote Similarity	NPC470077
0.6418	Remote Similarity	NPC125399
0.6418	Remote Similarity	NPC486522
0.6418	Remote Similarity	NPC470049
0.6377	Remote Similarity	NPC142361
0.6377	Remote Similarity	NPC212948
0.6377	Remote Similarity	NPC474684
0.6377	Remote Similarity	NPC479293
0.6377	Remote Similarity	NPC479294
0.6269	Remote Similarity	NPC470224
0.6056	Remote Similarity	NPC470375
0.6056	Remote Similarity	NPC470376
0.5972	Remote Similarity	NPC601194
0.5857	Remote Similarity	NPC486523
0.5735	Remote Similarity	NPC110923
0.5735	Remote Similarity	NPC74296
0.5733	Remote Similarity	NPC73506
0.5696	Remote Similarity	NPC609156
0.5694	Remote Similarity	NPC210268
0.5694	Remote Similarity	NPC190604
0.5676	Remote Similarity	NPC483384
0.5676	Remote Similarity	NPC484791
0.5676	Remote Similarity	NPC484790
0.5652	Remote Similarity	NPC328052
0.5616	Remote Similarity	NPC484789
0.5616	Remote Similarity	NPC484801
0.5616	Remote Similarity	NPC484786
0.5616	Remote Similarity	NPC484787
0.5616	Remote Similarity	NPC484788
0.5588	Remote Similarity	NPC1319
0.5541	Remote Similarity	NPC471293
0.5541	Remote Similarity	NPC324598
0.5541	Remote Similarity	NPC6190
0.5467	Remote Similarity	NPC5358
0.5467	Remote Similarity	NPC216260
0.5417	Remote Similarity	NPC165064
0.5405	Remote Similarity	NPC138536
0.5333	Remote Similarity	NPC475921
0.5333	Remote Similarity	NPC474704
0.527	Remote Similarity	NPC7260
0.527	Remote Similarity	NPC210037
0.527	Remote Similarity	NPC120968
0.527	Remote Similarity	NPC171203
0.527	Remote Similarity	NPC307426
0.527	Remote Similarity	NPC98442
0.527	Remote Similarity	NPC242468
0.527	Remote Similarity	NPC227467
0.527	Remote Similarity	NPC273621
0.5205	Remote Similarity	NPC477872
0.5068	Remote Similarity	NPC260992
0.5067	Remote Similarity	NPC51700
0.5067	Remote Similarity	NPC88716
0.5067	Remote Similarity	NPC68160
0.5067	Remote Similarity	NPC112866
0.5065	Remote Similarity	NPC479665
0.5065	Remote Similarity	NPC293081
0.5063	Remote Similarity	NPC39082
0.5063	Remote Similarity	NPC610107

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC262858 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6552
0.1-0.2	2490
0.2-0.3	97
0.3-0.4	10
0.4-0.5	1
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