NPASS Compound

Natural Product: NPC155192

Natural Product ID	NPC155192
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3Beta,23,28-Trihydroxy-12-Oleanene 3Beta-Caffeate
IUPAC Name	[(3S,4R,4aR,6aR,6bS,8aS,12aS,14aR,14bR)-4,8a-bis(hydroxymethyl)-4,6a,6b,11,11,14b-hexamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-yl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL503195
PubChem CID	10651525
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 101106 0 0 0 0 0 0 0 0999 V2000 -7.4360 -2.5982 1.4578 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0155 -1.8768 0.1798 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3558 -2.8250 -0.9620 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8044 -0.6095 0.0971 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1583 0.2897 -0.9101 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8283 0.8300 -0.3620 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.0573 1.2852 -1.5451 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6335 1.6547 -1.3098 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8566 0.6138 -0.5628 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4037 -0.4139 -1.6039 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6736 -0.1388 0.4106 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0278 -0.8453 1.3461 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5567 -0.9305 1.4795 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8322 -0.0126 0.5816 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5711 0.3544 1.0307 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6282 1.0777 2.3185 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3436 -0.9402 1.1892 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1510 -1.3310 0.0083 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1044 -0.2945 -0.4961 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6502 1.1168 -0.1960 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3567 1.7316 0.9570 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0356 1.9533 -1.4269 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4289 1.5008 -2.5730 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1650 1.0943 -0.1432 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4816 2.4136 -0.3213 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9413 2.1286 -0.7316 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6656 1.1806 0.1810 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1755 1.9694 1.3405 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4149 -0.4353 0.0495 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5135 -0.7162 -0.7409 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3270 -0.8460 -1.9697 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8747 -0.8635 -0.1780 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8723 -1.1332 -1.0001 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2491 -1.2990 -0.5572 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2158 -1.5851 -1.5297 C 0 0 0 0 0 0 0 0 0 0 0 0 11.5382 -1.7587 -1.2115 C 0 0 0 0 0 0 0 0 0 0 0 0 11.9072 -1.6447 0.1069 C 0 0 0 0 0 0 0 0 0 0 0 0 10.9874 -1.3657 1.0834 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6750 -1.1984 0.7291 C 0 0 0 0 0 0 0 0 0 0 0 0 11.3475 -1.2457 2.4353 O 0 0 0 0 0 0 0 0 0 0 0 0 13.2294 -1.8103 0.4857 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1430 -0.1985 0.4458 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.5517 -1.6155 0.1242 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2413 1.9790 0.5493 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9313 2.9660 -0.1374 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6395 -3.2850 1.7944 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6643 -1.8804 2.2573 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3735 -3.1919 1.2590 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3366 -2.6045 -1.4072 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5828 -2.7337 -1.7747 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3064 -3.8808 -0.6220 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8681 -0.1824 1.1128 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8195 -0.8675 -0.2821 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9878 -0.3000 -1.8327 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8579 1.1159 -1.1468 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1520 0.5084 -2.3396 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5727 2.1872 -1.9629 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5671 2.6775 -0.8981 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1646 1.7526 -2.3359 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3364 -1.4268 -1.1529 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2484 -0.4886 -2.3345 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5267 -0.1007 -2.1707 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6004 -1.4123 2.0808 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3139 -2.0095 1.2362 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3185 -0.8271 2.5561 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6575 -0.5728 -0.3901 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3044 0.9750 2.9140 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4259 0.6399 2.9841 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8528 2.1527 2.2710 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6842 -1.7933 1.4427 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0477 -0.8698 2.0710 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7630 -2.2166 0.3111 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4649 -1.7053 -0.7815 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1428 -0.4451 -1.6169 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9337 2.7019 1.2268 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4690 1.0299 1.7892 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4166 1.9638 0.6317 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1433 1.7496 -1.5387 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9718 3.0276 -1.2394 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0338 0.9378 -3.1112 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8574 0.4885 -1.0560 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9471 2.9129 -1.2224 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5861 3.1167 0.4977 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9332 1.8089 -1.7930 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4821 3.1146 -0.6853 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3874 2.7167 1.6703 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5489 1.3887 2.1931 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0160 2.6281 1.0370 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0674 -0.7580 0.8646 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6307 -1.2318 -2.0516 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9089 -1.6722 -2.5697 H 0 0 0 0 0 0 0 0 0 0 0 0 12.3100 -1.9809 -1.9405 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9636 -0.9793 1.5086 H 0 0 0 0 0 0 0 0 0 0 0 0 11.7740 -0.3497 2.6824 H 0 0 0 0 0 0 0 0 0 0 0 0 13.6862 -1.0330 0.9581 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4317 -0.0545 1.5290 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1061 -1.9200 -0.8658 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0526 -2.2723 0.8775 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9376 1.6151 1.3439 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3834 2.4171 1.0928 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3818 3.8117 -0.1139 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 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 6 9 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 1 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 1 20 22 1 0 22 23 1 0 20 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 1 19 29 1 0 29 30 1 0 30 31 2 0 30 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 35 36 1 0 36 37 2 0 37 38 1 0 38 39 2 0 38 40 1 0 37 41 1 0 11 42 1 0 42 43 1 0 6 44 1 1 44 45 1 0 43 2 1 0 42 6 1 0 27 9 1 0 39 34 1 0 27 14 1 0 24 15 1 0 1 46 1 0 1 47 1 0 1 48 1 0 3 49 1 0 3 50 1 0 3 51 1 0 4 52 1 0 4 53 1 0 5 54 1 0 5 55 1 0 7 56 1 0 7 57 1 0 8 58 1 0 8 59 1 0 10 60 1 0 10 61 1 0 10 62 1 0 12 63 1 0 13 64 1 0 13 65 1 0 14 66 1 6 16 67 1 0 16 68 1 0 16 69 1 0 17 70 1 0 17 71 1 0 18 72 1 0 18 73 1 0 19 74 1 6 21 75 1 0 21 76 1 0 21 77 1 0 22 78 1 0 22 79 1 0 23 80 1 0 24 81 1 6 25 82 1 0 25 83 1 0 26 84 1 0 26 85 1 0 28 86 1 0 28 87 1 0 28 88 1 0 32 89 1 0 33 90 1 0 35 91 1 0 36 92 1 0 39 93 1 0 40 94 1 0 41 95 1 0 42 96 1 1 43 97 1 0 43 98 1 0 44 99 1 0 44100 1 0 45101 1 0 M END

Standard InCHIKey	VEOYEUQHJXNXHF-YIEOTUJOSA-N
Standard InCHI	InChI=1S/C39H56O6/c1-34(2)17-19-39(24-41)20-18-37(5)26(27(39)22-34)9-11-31-35(3)15-14-32(36(4,23-40)30(35)13-16-38(31,37)6)45-33(44)12-8-25-7-10-28(42)29(43)21-25/h7-10,12,21,27,30-32,40-43H,11,13-20,22-24H2,1-6H3/b12-8+/t27-,30+,31+,32-,35-,36-,37+,38+,39+/m0/s1
SMILES	CC1(C)CC[C@@]2(CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)CC[C@@H]([C@@](C)(CO)[C@@H]5CC[C@@]34C)OC(=O)/C=C/c3ccc(c(c3)O)O)[C@@H]2C1)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	620.41	Volume:	668.684 ? Van der Waals volume.
Dense:	0.928	LogP:	5.379 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.36 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.536 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	34.0
TPSA:	107.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.116	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.059	Fsp³:	0.718
MCE-18:	161.866 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.947	Fluc inhibitor:	0.892 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.14 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.072 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.211	Promiscuous compounds:	0.125

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.697	MDCK Permeability:	-5.057
Pgp-inhibitor:	0.509	Pgp-substrate:	0.0
PAMPA:	0.975 ? 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%):	0.997	30% Bioavailability (F30%):	0.96
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.99	MRP1:	0.459
Plasma Protein Binding (PPB):	96.829%	Volume Distribution (VD):	-0.122
Fu:	3.219% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.038	BCRP inhibitor:	0.581
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.018	CYP2C19-substrate:	0.005
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.046
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.807 ? 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):

8.917

Half-life (T1/2):

0.985

ADMET: Toxicity

hERG Blockers:	0.053	hERG Blockers (10um):	0.282
Human Hepatotoxicity (H-HT):	0.629	Drug-induced Liver Injury (DILI):	0.663
AMES Toxicity:	0.603	Rat Oral Acute Toxicity:	0.207
Maximum Recommended Daily Dose:	0.497	Skin Sensitization:	1.0
Carcinogencity:	0.847	Eye Corrosion:	0.002
Eye Irritation:	0.353	Respiratory Toxicity:	0.457
Drug-induced Neurotoxicity:	0.045	Ototoxicity:	0.745
Hematotoxicity:	0.348	Drug-induced Nephrotoxicity:	0.856
Genotoxicity:	0.886	RPMI-8226 Immunitoxicity:	0.027
A549 Cytotoxicity:	0.86	Hek293 Cytotoxicity:	0.581
BCF:	1.401 ? 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:	4.541 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.285 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.577 ? 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
NPO29062	Hibiscus syriacus	Species	Malvaceae	Eukaryota	root bark	n.a.	n.a.	PMID[10346965]
NPO29062	Hibiscus syriacus	Species	Malvaceae	Eukaryota	n.a.	root	n.a.	PMID[10617409]
NPO29062	Hibiscus syriacus	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11575966]
NPO29062	Hibiscus syriacus	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29062	Hibiscus syriacus	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29062	Hibiscus syriacus	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29062	Hibiscus syriacus	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO29062	Hibiscus syriacus	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO29062	Hibiscus syriacus	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	1
ED50	9

Activity Type	# Activity
Cell line	9
Subcellular	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
NPT398	Cell line	UACC-62	Homo sapiens	ED50	=	2.3	ug ml-1	PMID[9358638]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	1.8	ug ml-1	PMID[23398362]
NPT370	Cell line	NCI-H23	Homo sapiens	ED50	=	1.7	ug ml-1	PMID[8864235]
NPT369	Cell line	ACHN	Homo sapiens	ED50	=	2.1	ug ml-1	DOI[10.1039/C4MD00203B]
NPT371	Cell line	UO-31	Homo sapiens	ED50	=	1.7	ug ml-1	DOI[10.1039/C4MD00203B]
NPT306	Cell line	PC-3	Homo sapiens	ED50	=	2.2	ug ml-1	DrugMatrix in vitro pharmacology data
NPT323	Cell line	SW-620	Homo sapiens	ED50	=	1.0	ug ml-1	DrugMatrix in vitro pharmacology data
NPT148	Cell line	HCT-15	Homo sapiens	ED50	=	1.3	ug ml-1	DrugMatrix in vitro pharmacology data
NPT374	Cell line	SF-539	Homo sapiens	ED50	=	2.0	ug ml-1	DrugMatrix in vitro pharmacology data
NPT1084	Subcellular	Liver microsomes	Rattus norvegicus	IC50	=	1.1	ug.mL-1	PMID[9358638]

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 NPC155192 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	8007
0.1-0.2	36877
0.2-0.3	4132
0.3-0.4	713
0.4-0.5	102
0.5-0.6	14
0.6-0.7	6
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
0.7191	Intermediate Similarity	NPC271494
0.7045	Intermediate Similarity	NPC182249
0.6667	Remote Similarity	NPC473591
0.6559	Remote Similarity	NPC22676
0.6154	Remote Similarity	NPC310621
0.6082	Remote Similarity	NPC482052
0.6049	Remote Similarity	NPC191965
0.6	Remote Similarity	NPC26045
0.5876	Remote Similarity	NPC477873
0.57	Remote Similarity	NPC132126
0.5686	Remote Similarity	NPC479745
0.5474	Remote Similarity	NPC148404
0.5474	Remote Similarity	NPC35212
0.5455	Remote Similarity	NPC469447
0.5437	Remote Similarity	NPC482051
0.5426	Remote Similarity	NPC478273
0.5294	Remote Similarity	NPC172311
0.5288	Remote Similarity	NPC610795
0.5229	Remote Similarity	NPC53520
0.52	Remote Similarity	NPC477874
0.5146	Remote Similarity	NPC605663
0.5048	Remote Similarity	NPC178093

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC155192 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4448
0.1-0.2	4643
0.2-0.3	55
0.3-0.4	2
0.4-0.5	2
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