NPASS Compound

Natural Product: NPC114378

Natural Product ID	NPC114378
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-O-Malonylepiocotillol Ii
IUPAC Name	3-[[(3R,5R,8R,9R,10R,13R,14R,17S)-17-[(2S,5R)-5-(2-hydroxypropan-2-yl)-2-methyloxolan-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-oxopropanoic acid
Synonyms	3-O-malonylepiocotillol II
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL224431
PubChem CID	44421634
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0002049] Terpene glycosides [CHEMONTID:0001580] Triterpene glycosides [CHEMONTID:0002358] Triterpene saponins

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 93 97 0 0 0 0 0 0 0 0999 V2000 -8.6100 2.3460 -2.3189 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.5394 1.4535 -1.2757 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6191 0.2304 -1.4944 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.3692 1.9430 0.1012 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9530 1.8085 0.5733 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6730 2.2118 1.7333 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9533 1.2723 -0.1891 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5986 1.1397 0.2530 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7590 1.9428 -0.6977 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4031 1.3566 -0.9819 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8802 0.5292 0.2048 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8389 -0.6591 0.2651 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2715 -0.3033 0.2897 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0351 -0.9656 -0.8695 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9032 -0.9026 1.5501 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4270 -1.6395 1.3483 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1161 -2.2494 0.8540 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0793 -1.2030 0.6324 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5470 -0.0201 -0.1631 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5462 1.0052 -0.2636 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8270 0.4381 -0.7792 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1653 -0.8433 -0.1322 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0164 -1.8406 -0.2244 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5894 -2.0658 -1.6400 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6138 -3.0692 0.3178 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0881 -2.9951 -0.0544 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2952 -1.6134 -0.6846 C 0 0 2 0 0 0 0 0 0 0 0 0 4.6513 -1.1056 -0.2685 C 0 0 2 0 0 0 0 0 0 0 0 0 5.7013 -2.0011 -0.9099 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8823 -1.0870 1.1973 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2936 0.3742 1.4334 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8315 0.7123 0.0592 C 0 0 1 0 0 0 0 0 0 0 0 0 4.8497 0.1830 -0.7620 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0677 2.1746 -0.1563 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0519 2.6323 0.6942 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6424 2.3061 -1.5740 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8345 3.0075 -0.0451 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4899 -0.8458 1.9771 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9324 1.4023 1.3963 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8771 1.9909 -3.2284 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6674 3.0054 0.1401 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0535 1.4071 0.7917 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5916 1.5449 1.2842 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6780 2.9857 -0.2786 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2786 2.0576 -1.6709 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7444 2.1845 -1.2429 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5067 0.6297 -1.8287 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6412 -1.2083 -0.7060 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0682 -0.5847 -0.8909 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0710 -2.0702 -0.6853 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5010 -0.7060 -1.7846 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3190 -0.6879 2.4472 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8920 -0.4139 1.6724 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1354 -1.9821 1.4055 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3461 -1.1887 2.3346 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1638 -2.4716 1.3025 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3621 -2.8745 0.0022 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7349 -2.9250 1.6699 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6748 -0.3981 -1.2252 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2264 1.7665 -1.0374 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7330 1.5784 0.6409 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6350 1.1797 -0.5023 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8801 0.4180 -1.9060 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3764 -0.6534 0.9381 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4723 -2.3504 -1.7555 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7991 -1.2528 -2.3336 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1588 -2.9543 -2.0504 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2037 -3.9503 -0.2619 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4504 -3.3113 1.3603 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6771 -3.1321 0.8550 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3901 -3.7776 -0.7680 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2962 -1.7576 -1.7738 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2438 -2.6525 -1.6709 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5070 -1.3961 -1.3485 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1991 -2.6332 -0.1172 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0565 -1.3836 1.8308 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7816 -1.6819 1.5155 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0437 0.4647 2.2288 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3397 0.9166 1.6615 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7849 0.1498 -0.0416 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0409 3.6408 0.7402 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6446 3.3466 -1.9201 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6906 1.8925 -1.4961 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0663 1.6121 -2.2098 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2231 2.9576 -0.9736 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2641 2.7858 0.8594 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1467 4.0796 0.0372 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3671 -0.8950 2.7129 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2298 -1.5584 2.3590 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9052 0.1510 2.0772 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9230 1.6647 1.8283 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3694 2.4245 1.1840 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4844 0.9574 2.2691 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 2 0 5 7 1 0 7 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 13 15 1 0 12 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 6 23 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 6 28 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 32 34 1 0 34 35 1 0 34 36 1 0 34 37 1 0 18 38 1 1 11 39 1 1 13 8 1 0 23 18 1 0 33 28 1 0 19 11 1 0 27 22 1 0 1 40 1 0 4 41 1 0 4 42 1 0 8 43 1 1 9 44 1 0 9 45 1 0 10 46 1 0 10 47 1 0 12 48 1 6 14 49 1 0 14 50 1 0 14 51 1 0 15 52 1 0 15 53 1 0 15 54 1 0 16 55 1 0 16 56 1 0 17 57 1 0 17 58 1 0 19 59 1 6 20 60 1 0 20 61 1 0 21 62 1 0 21 63 1 0 22 64 1 1 24 65 1 0 24 66 1 0 24 67 1 0 25 68 1 0 25 69 1 0 26 70 1 0 26 71 1 0 27 72 1 6 29 73 1 0 29 74 1 0 29 75 1 0 30 76 1 0 30 77 1 0 31 78 1 0 31 79 1 0 32 80 1 6 35 81 1 0 36 82 1 0 36 83 1 0 36 84 1 0 37 85 1 0 37 86 1 0 37 87 1 0 38 88 1 0 38 89 1 0 38 90 1 0 39 91 1 0 39 92 1 0 39 93 1 0 M END

Standard InCHIKey	PYEPYIQOBUHNRP-ZLPWZIBNSA-N
Standard InCHI	InChI=1S/C33H54O6/c1-28(2)22-12-17-32(7)23(30(22,5)15-13-24(28)38-27(36)19-26(34)35)10-9-20-21(11-16-31(20,32)6)33(8)18-14-25(39-33)29(3,4)37/h20-25,37H,9-19H2,1-8H3,(H,34,35)/t20-,21+,22+,23-,24-,25-,30+,31-,32-,33+/m1/s1
SMILES	OC(=O)CC(=O)O[C@@H]1CC[C@]2([C@H](C1(C)C)CC[C@@]1([C@@H]2CC[C@H]2[C@@]1(C)CC[C@@H]2[C@]1(C)CC[C@@H](O1)C(O)(C)C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	546.39	Volume:	584.01 ? Van der Waals volume.
Dense:	0.936	LogP:	3.882 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.574 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.147 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	27.0
TPSA:	93.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.292	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.919	Fsp³:	0.939
MCE-18:	108.906 ? 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:	0.888	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.002 ? 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:	0.351	Promiscuous compounds:	0.412

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.283	MDCK Permeability:	-5.055
Pgp-inhibitor:	0.389	Pgp-substrate:	0.0
PAMPA:	0.172 ? 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%):	0.001	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.24

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.031	MRP1:	0.939
Plasma Protein Binding (PPB):	98.097%	Volume Distribution (VD):	-0.314
Fu:	2.779% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.001
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.041	CYP1A2-substrate:	0.041
CYP2C19-inhibitor:	0.998	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.012	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.018
CYP3A4-inhibitor:	0.998	CYP3A4-substrate:	0.725
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.996
HLM stability:	0.322 ? 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):

2.091

Half-life (T1/2):

1.255

ADMET: Toxicity

hERG Blockers:	0.019	hERG Blockers (10um):	0.03
Human Hepatotoxicity (H-HT):	0.499	Drug-induced Liver Injury (DILI):	0.371
AMES Toxicity:	0.13	Rat Oral Acute Toxicity:	0.283
Maximum Recommended Daily Dose:	0.236	Skin Sensitization:	0.954
Carcinogencity:	0.73	Eye Corrosion:	0.213
Eye Irritation:	0.53	Respiratory Toxicity:	0.378
Drug-induced Neurotoxicity:	0.008	Ototoxicity:	0.664
Hematotoxicity:	0.473	Drug-induced Nephrotoxicity:	0.915
Genotoxicity:	0.633	RPMI-8226 Immunitoxicity:	0.028
A549 Cytotoxicity:	0.009	Hek293 Cytotoxicity:	0.123
BCF:	0.552 ? 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:	3.536 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.3 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.621 ? 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
NPO4138.1	Betula platyphylla var. japonica	Varieties	Betulaceae	Eukaryota	floral spikes	n.a.	n.a.	PMID[17346076]
NPO4138.1	Betula platyphylla var. japonica	Varieties	Betulaceae	Eukaryota	bark	n.a.	n.a.	PMID[9873651]
NPO4138.1	Betula platyphylla var. japonica	Varieties	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4138.1	Betula platyphylla var. japonica	Varieties	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4138.1	Betula platyphylla var. japonica	Varieties	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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	4

Activity Type	# Activity
Cell line	4

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
NPT91	Cell line	KB	Homo sapiens	IC50	=	60800.0	nM	PMID[17850214]
NPT111	Cell line	K562	Homo sapiens	IC50	=	57500.0	nM	PMID[18491867]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	64100.0	nM	PMID[16472241]
NPT407	Cell line	COLO 205	Homo sapiens	IC50	=	55600.0	nM	PMID[16472241]

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 NPC114378 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	20586
0.1-0.2	25547
0.2-0.3	3461
0.3-0.4	199
0.4-0.5	30
0.5-0.6	29
0.6-0.7	2
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
0.7778	Intermediate Similarity	NPC190940
0.75	Intermediate Similarity	NPC201607
0.7206	Intermediate Similarity	NPC103782
0.6338	Remote Similarity	NPC254572
0.6338	Remote Similarity	NPC229407
0.5915	Remote Similarity	NPC477285
0.5857	Remote Similarity	NPC245029
0.5857	Remote Similarity	NPC31302
0.5797	Remote Similarity	NPC91387
0.5797	Remote Similarity	NPC231680
0.5797	Remote Similarity	NPC270306
0.5775	Remote Similarity	NPC292458
0.5775	Remote Similarity	NPC217559
0.5775	Remote Similarity	NPC268578
0.5753	Remote Similarity	NPC286719
0.5753	Remote Similarity	NPC477286
0.5652	Remote Similarity	NPC488509
0.5556	Remote Similarity	NPC133596
0.5556	Remote Similarity	NPC11907
0.5405	Remote Similarity	NPC250687
0.5405	Remote Similarity	NPC48824
0.5405	Remote Similarity	NPC148740
0.5405	Remote Similarity	NPC102156
0.5342	Remote Similarity	NPC13494
0.5342	Remote Similarity	NPC488510
0.5316	Remote Similarity	NPC56777
0.5263	Remote Similarity	NPC269267
0.5195	Remote Similarity	NPC311642
0.5195	Remote Similarity	NPC164289
0.5195	Remote Similarity	NPC100366
0.5195	Remote Similarity	NPC471747
0.5195	Remote Similarity	NPC242771
0.5065	Remote Similarity	NPC488503
0.5062	Remote Similarity	NPC479791

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC114378 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5643
0.1-0.2	3407
0.2-0.3	94
0.3-0.4	5
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