NPASS Compound

Natural Product: NPC12774

Natural Product ID	NPC12774
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Methyl Betulinate
IUPAC Name	methyl (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-hydroxy-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysene-3a-carboxylate
Synonyms	betulinic acid methylester; Methyl betulinate
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL295602
PubChem CID	73493
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 84 88 0 0 0 0 0 0 0 0999 V2000 -3.9525 2.4833 -2.4731 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9919 2.2669 -1.1793 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0057 3.4186 -0.2562 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0220 0.8954 -0.6541 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2723 0.6819 0.2167 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7501 0.1400 1.5546 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4998 -0.5774 1.0638 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6166 -1.0197 2.1907 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2403 -1.3124 1.6843 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6875 -0.2655 0.7700 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4785 0.9621 1.6211 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6252 0.0751 -0.3763 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0290 1.1051 -1.2732 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4187 0.9656 -1.5783 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2424 0.4529 -0.4452 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6976 0.3531 -0.7582 C 0 0 1 0 0 0 0 0 0 0 0 0 2.9698 -0.2844 -2.0728 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2207 1.7946 -0.8525 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2847 2.0706 0.1806 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4138 1.0888 0.1034 C 0 0 1 0 0 0 0 0 0 0 0 0 4.8650 -0.2783 0.4168 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2784 -0.5664 1.8745 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5094 -1.3483 -0.4129 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3826 -0.2717 0.4119 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8398 -1.6569 0.7300 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4175 -1.4265 1.2206 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5925 -0.7720 0.1374 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2853 -1.8238 -0.8790 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0433 1.1709 -1.1214 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9127 0.5320 0.2432 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9626 -1.7563 0.3249 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7524 -2.0453 -0.8703 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7435 -2.6927 1.0318 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2353 -3.8585 0.4067 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9296 3.5011 -2.8851 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9397 1.6992 -3.2244 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0615 3.7889 -0.1018 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5163 3.1967 0.7004 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4952 4.2886 -0.7634 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0559 0.1485 -1.5035 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7795 1.6460 0.3903 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9397 -0.0174 -0.2841 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4530 -0.5682 2.0022 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5063 0.9878 2.2264 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0405 -2.0047 2.5504 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6520 -0.3642 3.0782 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5685 -1.3014 2.5974 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1881 -2.3402 1.3142 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2875 0.9917 2.4140 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5992 1.9104 1.0774 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4611 0.9082 2.2309 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8258 -0.8121 -0.9743 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3131 2.1562 -0.9762 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5512 0.9813 -2.2740 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5877 0.4207 -2.5308 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7987 2.0094 -1.7981 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1811 1.2438 0.3638 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0571 -0.3410 -2.2644 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4950 -1.2366 -2.2716 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5933 0.4297 -2.8652 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6574 2.0167 -1.8360 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4202 2.5422 -0.6858 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8894 2.2092 1.1973 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7188 3.0726 -0.1073 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1783 1.4307 0.8626 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2687 -0.1228 2.0963 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3974 -1.6659 2.0300 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5063 -0.2284 2.5790 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8010 -2.0979 -0.8163 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2604 -1.9622 0.1697 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1454 -0.8889 -1.2271 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0658 0.3473 1.3093 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4446 -2.0486 1.5740 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9153 -2.3600 -0.0908 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4547 -0.8714 2.1541 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9534 -2.4114 1.4292 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1378 -1.4627 -1.8983 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0806 -2.6260 -0.9322 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6403 -2.4245 -0.6373 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9919 0.9603 -1.0137 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6829 1.3540 0.9748 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6457 -4.7613 0.6734 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2103 -3.7885 -0.6959 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2631 -4.0358 0.7573 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 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 1 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 6 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 21 23 1 0 21 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 6 20 29 1 0 12 30 1 0 7 31 1 6 31 32 2 0 31 33 1 0 33 34 1 0 30 4 1 0 30 7 1 0 27 10 1 0 27 15 1 0 24 16 1 0 1 35 1 0 1 36 1 0 3 37 1 0 3 38 1 0 3 39 1 0 4 40 1 6 5 41 1 0 5 42 1 0 6 43 1 0 6 44 1 0 8 45 1 0 8 46 1 0 9 47 1 0 9 48 1 0 11 49 1 0 11 50 1 0 11 51 1 0 12 52 1 6 13 53 1 0 13 54 1 0 14 55 1 0 14 56 1 0 15 57 1 1 17 58 1 0 17 59 1 0 17 60 1 0 18 61 1 0 18 62 1 0 19 63 1 0 19 64 1 0 20 65 1 1 22 66 1 0 22 67 1 0 22 68 1 0 23 69 1 0 23 70 1 0 23 71 1 0 24 72 1 1 25 73 1 0 25 74 1 0 26 75 1 0 26 76 1 0 28 77 1 0 28 78 1 0 28 79 1 0 29 80 1 0 30 81 1 1 34 82 1 0 34 83 1 0 34 84 1 0 M END

Standard InCHIKey	XNZIMRUZBOZIBC-JVRMVBBZSA-N
Standard InCHI	InChI=1S/C31H50O3/c1-19(2)20-11-16-31(26(33)34-8)18-17-29(6)21(25(20)31)9-10-23-28(5)14-13-24(32)27(3,4)22(28)12-15-30(23,29)7/h20-25,32H,1,9-18H2,2-8H3/t20-,21+,22-,23+,24-,25+,28-,29+,30+,31-/m0/s1
SMILES	C=C(C)[C@@H]1CC[C@@]2(CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@@H](C(C)(C)[C@@H]5CC[C@@]34C)O)[C@@H]12)C(=O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	470.38	Volume:	523.047 ? Van der Waals volume.
Dense:	0.899	LogP:	5.749 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.736 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.204 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	27.0
TPSA:	46.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.343	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.714	Fsp³:	0.903
MCE-18:	103.051 ? 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:	0.971	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? 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:	0.421	Promiscuous compounds:	0.348

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.009	MDCK Permeability:	-4.864
Pgp-inhibitor:	0.124	Pgp-substrate:	0.12
PAMPA:	0.119 ? 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%):	0.41	30% Bioavailability (F30%):	0.614
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.867	MRP1:	0.988
Plasma Protein Binding (PPB):	97.578%	Volume Distribution (VD):	0.139
Fu:	2.886% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.764
BSEP inhibitor:	0.89

ADMET: Metabolism

CYP1A2-inhibitor:	0.011	CYP1A2-substrate:	0.222
CYP2C19-inhibitor:	0.983	CYP2C19-substrate:	0.292
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.074	CYP2D6-substrate:	0.065
CYP3A4-inhibitor:	0.82	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.986
HLM stability:	0.336 ? 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):

10.031

Half-life (T1/2):

0.43

ADMET: Toxicity

hERG Blockers:	0.16	hERG Blockers (10um):	0.301
Human Hepatotoxicity (H-HT):	0.68	Drug-induced Liver Injury (DILI):	0.41
AMES Toxicity:	0.27	Rat Oral Acute Toxicity:	0.374
Maximum Recommended Daily Dose:	0.727	Skin Sensitization:	0.929
Carcinogencity:	0.9	Eye Corrosion:	0.144
Eye Irritation:	0.745	Respiratory Toxicity:	0.961
Drug-induced Neurotoxicity:	0.089	Ototoxicity:	0.421
Hematotoxicity:	0.446	Drug-induced Nephrotoxicity:	0.554
Genotoxicity:	0.574	RPMI-8226 Immunitoxicity:	0.038
A549 Cytotoxicity:	0.377	Hek293 Cytotoxicity:	0.407
BCF:	2.291 ? 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:	4.33 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.465 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.097 ? 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
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1007/s11240-015-0798-z]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.fitote.2006.01.011]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.jarmap.2018.11.004]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.plaphy.2005.07.013]
NPO2270	Euptelea polyandra	Species	Eupteleaceae	Eukaryota	n.a.	bark	n.a.	DOI[10.1021/np50040a042]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1078/0176-1617-00195]
NPO24749	Abutilon indicum	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1080/11263504.2021.1891151]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1155/2014/609649]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10757735]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14735439]
NPO21341	Morus macroura	Species	Moraceae	Eukaryota	n.a.	stem	n.a.	PMID[15467233]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	callus	n.a.	PMID[15715262]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18220354]
NPO2270	Euptelea polyandra	Species	Eupteleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2832544]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28445039]
NPO12957	Piper auritum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28704049]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	Roots	n.a.	n.a.	PMID[30024167]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32560389]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36336219]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38217369]
NPO43006	Achillea milefollium	Genus	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38611571]
NPO1407	Enceliopsis nudicaulis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23598	Hedera rhombea	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4781	Diospyros discolor	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7212	Ceratiola ericoides	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21792	Penicillium brefeldianum	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12957	Piper auritum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15321	Nicotiana clevelandii	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21341	Morus macroura	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24749	Abutilon indicum	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21341	Morus macroura	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23598	Hedera rhombea	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24749	Abutilon indicum	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO675	Dioscorea tenuipes	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24749	Abutilon indicum	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2270	Euptelea polyandra	Species	Eupteleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21980.1	Narcissus hispanicus subsp. bujei	Subspecies	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23598	Hedera rhombea	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21341	Morus macroura	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12957	Piper auritum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21792	Penicillium brefeldianum	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12136	Myrica serrata	Species	Myricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24302	Angylocalyx oligophyllus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21341	Morus macroura	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4781	Diospyros discolor	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12627	Anzia gracilis	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21291	Vernicia montana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24749	Abutilon indicum	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24424	Tricalysia okelensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2270	Euptelea polyandra	Species	Eupteleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15321	Nicotiana clevelandii	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6912	Amaranthus hybrid	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7551	Lycoperdon capitatum	Species	Lycoperdaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7212	Ceratiola ericoides	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21980.1	Narcissus hispanicus subsp. bujei	Subspecies	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23598	Hedera rhombea	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1407	Enceliopsis nudicaulis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO675	Dioscorea tenuipes	Species	Dioscoreaceae	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
NPO43006	Achillea milefollium	n.a.	n.a.	226.15 Â± 77.43	n.a.	n.a.	Âµg/g	PMID[38611571]
NPO43006	Achillea milefollium	n.a.	n.a.	239.78 Â± 75.7	n.a.	n.a.	Âµg/g	PMID[38611571]
NPO43006	Achillea milefollium	n.a.	n.a.	230.81 Â± 63.13	n.a.	n.a.	Âµg/g	PMID[38611571]
NPO43006	Achillea milefollium	n.a.	n.a.	225.74 Â± 63.13	n.a.	n.a.	Âµg/g	PMID[38611571]
NPO43006	Achillea milefollium	n.a.	n.a.	23.84 Â± 6.72	n.a.	n.a.	Âµg/g	PMID[38611571]
NPO43006	Achillea milefollium	n.a.	n.a.	19.12 Â± 2.69	n.a.	n.a.	Âµg/g	PMID[38611571]

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
EC50	2
Efficacy	1
IC50	27
Ki	1
ED50	3
Activity	10
GI50	52

Activity Type	# Activity
Individual protein	5
Cell line	81
Organism	1
Others	5
Non-molecular	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1217	Individual protein	Botulinum neurotoxin type A	Clostridium botulinum	IC50	<	100000.0	nM	PMID[21421315]
NPT1218	Individual protein	Carbonic anhydrase II	Bos taurus	Ki	>	50000.0	nM	PMID[25147151]
NPT745	Individual protein	G-protein coupled bile acid receptor 1	Homo sapiens	EC50	>	10000.0	nM	PMID[19911773]
NPT745	Individual protein	G-protein coupled bile acid receptor 1	Homo sapiens	Efficacy	=	0.0	%	PMID[19911773]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	EC50	=	0.0	nM	PMID[19911773]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT147	Cell line	SK-MEL-2	Homo sapiens	ED50	=	8.3	ug ml-1	PMID[9873420]
NPT91	Cell line	KB	Homo sapiens	ED50	=	11.8	ug ml-1	PMID[9873420]
NPT80	Cell line	Raji	Homo sapiens	Activity	>	80.0	%	PMID[2832544]
NPT80	Cell line	Raji	Homo sapiens	Activity	=	80.0	%	PMID[2832544]
NPT80	Cell line	Raji	Homo sapiens	Activity	=	100.0	%	PMID[2832544]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	109000.0	nM	PMID[15270560]
NPT111	Cell line	K562	Homo sapiens	IC50	=	65000.0	nM	PMID[15270560]
NPT111	Cell line	K562	Homo sapiens	IC50	=	71000.0	nM	PMID[15270560]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	61000.0	nM	PMID[15270560]
NPT404	Cell line	CCRF-CEM	Homo sapiens	IC50	=	150000.0	nM	PMID[15270560]
NPT319	Cell line	B16	Mus musculus	ED50	=	2.5	uM	PMID[12027734]
NPT319	Cell line	B16	Mus musculus	IC50	=	4900.0	nM	PMID[12027734]
NPT1215	Cell line	8505C	Homo sapiens	IC50	=	23670.0	nM	PMID[20451375]
NPT762	Cell line	A-431	Homo sapiens	IC50	=	26990.0	nM	PMID[20451375]
NPT81	Cell line	A549	Homo sapiens	IC50	=	20630.0	nM	PMID[20451375]
NPT179	Cell line	A2780	Homo sapiens	IC50	=	29310.0	nM	PMID[20451375]
NPT579	Cell line	DLD-1	Homo sapiens	IC50	=	45860.0	nM	PMID[20451375]
NPT1216	Cell line	FaDu	Homo sapiens	IC50	=	20330.0	nM	PMID[20451375]
NPT180	Cell line	HCT-8	Homo sapiens	IC50	=	17250.0	nM	PMID[20451375]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	20470.0	nM	PMID[20451375]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	30720.0	nM	PMID[20451375]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	24390.0	nM	PMID[20451375]
NPT660	Cell line	SW480	Homo sapiens	IC50	=	17920.0	nM	PMID[20451375]
NPT763	Cell line	SW-1736	Homo sapiens	IC50	=	32100.0	nM	PMID[20451375]
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	16106.46	nM	PubChem BioAssay data set
NPT367	Cell line	MDA-N	Homo sapiens	GI50	n.a.	18155.16	nM	PubChem BioAssay data set
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	30338.91	nM	PubChem BioAssay data set
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	22803.42	nM	PubChem BioAssay data set
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	16943.38	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	35481.34	nM	PubChem BioAssay data set
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	19408.86	nM	PubChem BioAssay data set
NPT90	Cell line	DU-145	Homo sapiens	GI50	n.a.	39810.72	nM	PubChem BioAssay data set
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	13740.42	nM	PubChem BioAssay data set
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	18836.49	nM	PubChem BioAssay data set
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	22490.55	nM	PubChem BioAssay data set
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	18879.91	nM	PubChem BioAssay data set
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	20511.62	nM	PubChem BioAssay data set
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	19815.27	nM	PubChem BioAssay data set
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	18793.17	nM	PubChem BioAssay data set
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	18836.49	nM	PubChem BioAssay data set
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	17782.79	nM	PubChem BioAssay data set
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	19010.78	nM	PubChem BioAssay data set
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	26791.68	nM	PubChem BioAssay data set
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	21527.82	nM	PubChem BioAssay data set
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	18663.8	nM	PubChem BioAssay data set
NPT385	Cell line	SR	Homo sapiens	GI50	n.a.	32284.94	nM	PubChem BioAssay data set
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	n.a.	34040.82	nM	PubChem BioAssay data set
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	19633.6	nM	PubChem BioAssay data set
NPT384	Cell line	TK-10	Homo sapiens	GI50	n.a.	10000.0	nM	PubChem BioAssay data set
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	18923.44	nM	PubChem BioAssay data set
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	15559.66	nM	PubChem BioAssay data set
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	35399.73	nM	PubChem BioAssay data set
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	19453.6	nM	PubChem BioAssay data set
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	18365.38	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	17660.38	nM	PubChem BioAssay data set
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	21627.19	nM	PubChem BioAssay data set
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	20511.62	nM	PubChem BioAssay data set
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	21428.91	nM	PubChem BioAssay data set
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	17418.07	nM	PubChem BioAssay data set
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	21677.04	nM	PubChem BioAssay data set
NPT83	Cell line	MCF7	Homo sapiens	GI50	n.a.	19364.22	nM	PubChem BioAssay data set
NPT306	Cell line	PC-3	Homo sapiens	GI50	n.a.	16710.91	nM	PubChem BioAssay data set
NPT396	Cell line	T47D	Homo sapiens	GI50	n.a.	11994.99	nM	PubChem BioAssay data set
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	18492.69	nM	PubChem BioAssay data set
NPT400	Cell line	MDA-MB-435	Homo sapiens	GI50	n.a.	20989.4	nM	PubChem BioAssay data set
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	20796.97	nM	PubChem BioAssay data set
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	18071.74	nM	PubChem BioAssay data set
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	18407.72	nM	PubChem BioAssay data set
NPT402	Cell line	Hs-578T	Homo sapiens	GI50	n.a.	21627.19	nM	PubChem BioAssay data set
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	19275.25	nM	PubChem BioAssay data set
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	19724.23	nM	PubChem BioAssay data set
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	19408.86	nM	PubChem BioAssay data set
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	n.a.	19952.62	nM	PubChem BioAssay data set
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	22335.72	nM	PubChem BioAssay data set
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	20464.45	nM	PubChem BioAssay data set
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	14521.12	nM	PubChem BioAssay data set
NPT179	Cell line	A2780	Homo sapiens	IC50	=	16270.0	nM	PMID[23973824]
NPT1215	Cell line	8505C	Homo sapiens	IC50	=	17170.0	nM	PMID[23973824]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	16930.0	nM	PMID[23973824]
NPT81	Cell line	A549	Homo sapiens	IC50	=	17170.0	nM	PMID[23973824]
NPT856	Organism	Semliki forest virus	Semliki forest virus	Activity	=	68.0	%	PMID[19839605]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	28750.0	nM	PMID[20451375]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	18510.0	nM	PMID[20451375]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	23260.0	nM	PMID[20451375]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	16930.0	nM	PMID[23973824]
NPT2	Others	Unspecified	n.a.	Activity	=	0.0	%	PMID[2832544]
NPT2	Others	Unspecified	n.a.	Activity	=	100.0	%	PMID[2832544]
NPT2	Others	Unspecified	n.a.	Activity	=	71.5	%	PMID[2832544]

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 NPC12774 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	18704
0.1-0.2	26039
0.2-0.3	4360
0.3-0.4	584
0.4-0.5	94
0.5-0.6	50
0.6-0.7	13
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.807	Intermediate Similarity	NPC33768
0.7222	Intermediate Similarity	NPC192638
0.7222	Intermediate Similarity	NPC25511
0.7222	Intermediate Similarity	NPC600137
0.7193	Intermediate Similarity	NPC74595
0.7193	Intermediate Similarity	NPC264665
0.6885	Remote Similarity	NPC607755
0.6842	Remote Similarity	NPC231256
0.6842	Remote Similarity	NPC178383
0.678	Remote Similarity	NPC63020
0.661	Remote Similarity	NPC246956
0.661	Remote Similarity	NPC269396
0.6557	Remote Similarity	NPC98270
0.6379	Remote Similarity	NPC104387
0.6271	Remote Similarity	NPC248830
0.6271	Remote Similarity	NPC212241
0.6167	Remote Similarity	NPC93662
0.6094	Remote Similarity	NPC481321
0.6066	Remote Similarity	NPC119355
0.5932	Remote Similarity	NPC97534
0.5932	Remote Similarity	NPC195155
0.5873	Remote Similarity	NPC603388
0.5846	Remote Similarity	NPC483720
0.5833	Remote Similarity	NPC78067
0.5833	Remote Similarity	NPC144075
0.5833	Remote Similarity	NPC278091
0.5833	Remote Similarity	NPC202540
0.5833	Remote Similarity	NPC301226
0.5738	Remote Similarity	NPC42853
0.5714	Remote Similarity	NPC232112
0.569	Remote Similarity	NPC142712
0.5667	Remote Similarity	NPC185536
0.5652	Remote Similarity	NPC480563
0.5645	Remote Similarity	NPC5767
0.5645	Remote Similarity	NPC475742
0.56	Remote Similarity	NPC473844
0.5593	Remote Similarity	NPC480925
0.5593	Remote Similarity	NPC48079
0.5574	Remote Similarity	NPC91573
0.55	Remote Similarity	NPC606606
0.5484	Remote Similarity	NPC58631
0.5484	Remote Similarity	NPC237460
0.5469	Remote Similarity	NPC126993
0.5455	Remote Similarity	NPC201406
0.5455	Remote Similarity	NPC289486
0.5455	Remote Similarity	NPC264317
0.5455	Remote Similarity	NPC294438
0.5397	Remote Similarity	NPC296701
0.5397	Remote Similarity	NPC201725
0.5397	Remote Similarity	NPC218616
0.5385	Remote Similarity	NPC49599
0.5385	Remote Similarity	NPC49627
0.5373	Remote Similarity	NPC112009
0.5323	Remote Similarity	NPC245869
0.5323	Remote Similarity	NPC240235
0.5323	Remote Similarity	NPC14112
0.5303	Remote Similarity	NPC477577
0.5231	Remote Similarity	NPC298168
0.5231	Remote Similarity	NPC143133
0.5195	Remote Similarity	NPC91583
0.5161	Remote Similarity	NPC102708
0.5156	Remote Similarity	NPC211009
0.5139	Remote Similarity	NPC475416
0.5077	Remote Similarity	NPC305835
0.5077	Remote Similarity	NPC57469
0.5077	Remote Similarity	NPC86305
0.5077	Remote Similarity	NPC212879
0.5075	Remote Similarity	NPC471900
0.5075	Remote Similarity	NPC477578

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC12774 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6669
0.1-0.2	2400
0.2-0.3	74
0.3-0.4	6
0.4-0.5	0
0.5-0.6	1
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
0.5455	Remote Similarity	NPD7520	Phase 1

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