NPASS Compound

Natural Product: NPC471567

Natural Product ID	NPC471567
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-Epicalamistrin
IUPAC Name	[(1R,3R)-3-hydroxy-1-[(2R,5R)-5-[(1R)-1-hydroxytridecyl]oxolan-2-yl]-15-(2-methyl-5-oxo-2H-furan-4-yl)pentadecyl] acetate
Synonyms	2-Epicalamistrin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL258182
PubChem CID	24760994
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0001334] Fatty alcohols [CHEMONTID:0002518] Annonaceous acetogenins

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 116117 0 0 0 0 0 0 0 0999 V2000 -14.3388 -1.6685 3.0965 C 0 0 0 0 0 0 0 0 0 0 0 0 -13.1970 -2.6588 3.1648 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.3331 -2.5333 1.9170 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.7683 -1.1541 1.8210 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.9050 -0.9914 0.5820 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.7486 -1.9354 0.5734 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9029 -1.7740 -0.6652 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3166 -0.4051 -0.8138 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4832 -0.2442 -2.0415 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3078 -1.1455 -2.1568 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2880 -1.0371 -1.0782 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6783 0.3432 -0.9723 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0033 0.7579 -2.2596 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4333 2.1388 -2.0409 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8422 2.7529 -3.2894 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7204 3.5732 -2.6199 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2403 2.4838 -1.6496 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4515 2.0800 -1.0893 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3459 3.0806 -0.5862 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8715 3.7276 -1.1518 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7970 2.8839 -1.9299 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3938 1.7583 -1.1316 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1933 2.3192 0.0025 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8522 1.2421 0.8353 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7795 0.3834 -0.0005 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8712 1.1517 -0.6539 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8409 1.8551 0.1737 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7677 1.1952 1.0958 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8076 0.2825 0.6201 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5404 -1.0091 -0.0055 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9129 -2.0761 0.7964 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6302 -2.6324 1.9671 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8826 -3.3956 1.7508 C 0 0 0 0 0 0 0 0 0 0 0 0 11.0519 -2.7277 1.1606 C 0 0 0 0 0 0 0 0 0 0 0 0 11.6722 -3.0263 0.0330 C 0 0 0 0 0 0 0 0 0 0 0 0 12.7938 -2.1288 -0.2169 C 0 0 0 0 0 0 0 0 0 0 0 0 12.8826 -1.3157 0.9133 O 0 0 0 0 0 0 0 0 0 0 0 0 11.8301 -1.6142 1.7468 C 0 0 0 0 0 0 0 0 0 0 0 0 11.5587 -1.0311 2.8546 O 0 0 0 0 0 0 0 0 0 0 0 0 14.0559 -2.9725 -0.2802 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2816 2.4230 -3.1482 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0610 2.1850 0.4427 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5117 2.3630 1.7627 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2043 3.4062 1.9603 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1938 1.3950 2.8346 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9992 -0.1131 -2.6574 O 0 0 0 0 0 0 0 0 0 0 0 0 -14.1744 -0.8608 3.8342 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.4222 -1.1884 2.0883 H 0 0 0 0 0 0 0 0 0 0 0 0 -15.2933 -2.2230 3.2959 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.5660 -3.7182 3.1708 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.5500 -2.4676 4.0313 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.5544 -3.3292 1.9709 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.9776 -2.7281 1.0318 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1169 -0.9604 2.7231 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.5605 -0.4054 1.8716 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.5199 -1.1525 -0.3240 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.5325 0.0532 0.5309 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0392 -2.9907 0.6672 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0617 -1.7159 1.4435 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1201 -2.5706 -0.6094 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5033 -2.0339 -1.5725 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8109 -0.0609 0.1078 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1860 0.3049 -0.9431 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1701 0.8370 -2.0885 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1259 -0.3738 -2.9474 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6795 -2.1955 -2.2199 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8617 -0.9526 -3.1768 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8301 -1.2002 -0.1027 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4996 -1.7852 -1.1902 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4474 1.0923 -0.7516 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9005 0.2884 -0.1856 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7362 0.7638 -3.1100 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2769 2.8300 -1.7450 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5138 3.4065 -3.8395 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3490 1.9615 -3.8522 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2431 4.3766 -2.0794 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9709 3.9033 -3.3238 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7543 1.7145 -2.2669 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9666 3.9061 -0.1121 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4445 4.2186 -0.3096 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6039 4.6197 -1.7973 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6819 3.5286 -2.2571 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0030 1.0774 -1.7786 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5610 1.1175 -0.7773 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5196 2.8577 0.6940 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9369 3.0725 -0.3247 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4264 1.7093 1.6262 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0928 0.5790 1.2773 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2425 -0.1842 -0.7801 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1923 -0.3593 0.7017 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3305 0.5524 -1.4355 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3437 1.9827 -1.2748 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5118 2.4389 -0.5644 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3834 2.7307 0.7425 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1486 0.7649 1.9370 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3151 2.0370 1.6463 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5499 0.0808 1.4699 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4872 0.8578 -0.1023 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4991 -1.4505 -0.4301 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9212 -0.9310 -0.9571 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8206 -1.8932 1.0252 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8149 -2.9654 0.0697 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9459 -3.3511 2.5379 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7811 -1.7810 2.6910 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1727 -3.9121 2.7236 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6189 -4.2422 1.0324 H 0 0 0 0 0 0 0 0 0 0 0 0 11.3721 -3.8413 -0.6142 H 0 0 0 0 0 0 0 0 0 0 0 0 12.6725 -1.5355 -1.1604 H 0 0 0 0 0 0 0 0 0 0 0 0 14.8224 -2.4682 -0.9379 H 0 0 0 0 0 0 0 0 0 0 0 0 13.8702 -4.0000 -0.6114 H 0 0 0 0 0 0 0 0 0 0 0 0 14.5148 -3.0125 0.7266 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9125 1.6920 -3.4388 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1211 0.9464 3.2478 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5068 0.6492 2.4090 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3940 1.9139 3.6437 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9721 -0.2167 -3.6508 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 1 0 6 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 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 2 0 35 36 1 0 36 37 1 0 37 38 1 0 38 39 2 0 36 40 1 0 21 41 1 0 19 42 1 0 42 43 1 0 43 44 2 0 43 45 1 0 13 46 1 0 18 14 1 0 38 34 1 0 1 47 1 0 1 48 1 0 1 49 1 0 2 50 1 0 2 51 1 0 3 52 1 0 3 53 1 0 4 54 1 0 4 55 1 0 5 56 1 0 5 57 1 0 6 58 1 0 6 59 1 0 7 60 1 0 7 61 1 0 8 62 1 0 8 63 1 0 9 64 1 0 9 65 1 0 10 66 1 0 10 67 1 0 11 68 1 0 11 69 1 0 12 70 1 0 12 71 1 0 13 72 1 0 14 73 1 0 15 74 1 0 15 75 1 0 16 76 1 0 16 77 1 0 17 78 1 0 19 79 1 0 20 80 1 0 20 81 1 0 21 82 1 0 22 83 1 0 22 84 1 0 23 85 1 0 23 86 1 0 24 87 1 0 24 88 1 0 25 89 1 0 25 90 1 0 26 91 1 0 26 92 1 0 27 93 1 0 27 94 1 0 28 95 1 0 28 96 1 0 29 97 1 0 29 98 1 0 30 99 1 0 30100 1 0 31101 1 0 31102 1 0 32103 1 0 32104 1 0 33105 1 0 33106 1 0 35107 1 0 36108 1 0 40109 1 0 40110 1 0 40111 1 0 41112 1 0 45113 1 0 45114 1 0 45115 1 0 46116 1 0 M END

Standard InCHIKey	FPQIHOHGIGXPEO-SCBCSMBVSA-N
Standard InCHI	InChI=1S/C39H70O7/c1-4-5-6-7-8-9-14-17-20-23-26-35(42)36-27-28-37(46-36)38(45-32(3)40)30-34(41)25-22-19-16-13-11-10-12-15-18-21-24-33-29-31(2)44-39(33)43/h29,31,34-38,41-42H,4-28,30H2,1-3H3/t31?,34-,35-,36-,37-,38-/m1/s1
SMILES	CCCCCCCCCCCCC(C1CCC(O1)C(CC(CCCCCCCCCCCCC2=CC(OC2=O)C)O)OC(=O)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	650.51	Volume:	719.609 ? Van der Waals volume.
Dense:	0.904	LogP:	8.737 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.938 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.502 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	30.0	Rigid Bonds:	12.0
TPSA:	102.29 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.061	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.556	Fsp³:	0.897
MCE-18:	32.027 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.644	Fluc inhibitor:	0.025 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.025 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.349	Promiscuous compounds:	0.008

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.243	MDCK Permeability:	-4.795
Pgp-inhibitor:	0.0	Pgp-substrate:	0.178
PAMPA:	0.014 ? 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):	0.999
20% Bioavailability (F20%):	0.998	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.999
Plasma Protein Binding (PPB):	98.684%	Volume Distribution (VD):	1.065
Fu:	1.422% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.303
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.476
BSEP inhibitor:	0.459

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.589
CYP2C19-inhibitor:	0.561	CYP2C19-substrate:	0.011
CYP2C9-inhibitor:	0.979	CYP2C9-substrate:	0.05
CYP2D6-inhibitor:	0.19	CYP2D6-substrate:	0.85
CYP3A4-inhibitor:	0.063	CYP3A4-substrate:	0.901
CYP2B6-substrate:	0.003	CYP2C8-inhibitor:	0.998
HLM stability:	0.121 ? 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):

5.042

Half-life (T1/2):

1.818

ADMET: Toxicity

hERG Blockers:	0.798	hERG Blockers (10um):	0.939
Human Hepatotoxicity (H-HT):	0.567	Drug-induced Liver Injury (DILI):	0.123
AMES Toxicity:	0.029	Rat Oral Acute Toxicity:	0.052
Maximum Recommended Daily Dose:	0.777	Skin Sensitization:	0.999
Carcinogencity:	0.056	Eye Corrosion:	0.0
Eye Irritation:	0.108	Respiratory Toxicity:	0.734
Drug-induced Neurotoxicity:	0.019	Ototoxicity:	0.852
Hematotoxicity:	0.023	Drug-induced Nephrotoxicity:	0.622
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.06
A549 Cytotoxicity:	0.814	Hek293 Cytotoxicity:	0.434
BCF:	0.253 ? 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:	5.083 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.955 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.291 ? 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
NPO33316	ampelocissus sp.	Species	Vitaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18177007]

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
GI50	7

Activity Type	# Activity
Cell line	7

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
NPT168	Cell line	P388	Mus musculus	GI50	=	0.014	ug.mL-1	PMID[19939516]
NPT1081	Cell line	BXPC-3	Homo sapiens	GI50	=	7.3	ug.mL-1	PMID[19939516]
NPT83	Cell line	MCF7	Homo sapiens	GI50	=	0.12	ug.mL-1	PMID[19939516]
NPT395	Cell line	SF-268	Homo sapiens	GI50	=	11.9	ug.mL-1	PMID[20044260]
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	=	0.2	ug.mL-1	PMID[19969457]
NPT575	Cell line	KM-20L2	Homo sapiens	GI50	=	0.034	ug.mL-1	PMID[19969457]
NPT90	Cell line	DU-145	Homo sapiens	GI50	=	0.0065	ug.mL-1	PMID[23347584]

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 NPC471567 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	17929
0.1-0.2	29131
0.2-0.3	2498
0.3-0.4	71
0.4-0.5	35
0.5-0.6	64
0.6-0.7	49
0.7-0.8	0
0.8-0.85	19
0.85-0.9	3
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC120398
0.902	High Similarity	NPC89001
0.8571	High Similarity	NPC473156
0.8571	High Similarity	NPC282815
0.8571	High Similarity	NPC600956
0.84	Intermediate Similarity	NPC473671
0.84	Intermediate Similarity	NPC475268
0.84	Intermediate Similarity	NPC470400
0.84	Intermediate Similarity	NPC77871
0.84	Intermediate Similarity	NPC9678
0.84	Intermediate Similarity	NPC319036
0.84	Intermediate Similarity	NPC605867
0.8333	Intermediate Similarity	NPC25764
0.8333	Intermediate Similarity	NPC235809
0.8333	Intermediate Similarity	NPC39279
0.8333	Intermediate Similarity	NPC39167
0.8333	Intermediate Similarity	NPC292809
0.8333	Intermediate Similarity	NPC202055
0.8333	Intermediate Similarity	NPC606804
0.8333	Intermediate Similarity	NPC607425
0.8333	Intermediate Similarity	NPC608574
0.8235	Intermediate Similarity	NPC132940
0.82	Intermediate Similarity	NPC610454
0.8077	Intermediate Similarity	NPC20533
0.7843	Intermediate Similarity	NPC473649
0.7843	Intermediate Similarity	NPC154097
0.7843	Intermediate Similarity	NPC159750
0.7843	Intermediate Similarity	NPC73248
0.7843	Intermediate Similarity	NPC470401
0.7692	Intermediate Similarity	NPC219652
0.7692	Intermediate Similarity	NPC473840
0.7692	Intermediate Similarity	NPC604764
0.76	Intermediate Similarity	NPC475159
0.76	Intermediate Similarity	NPC131002
0.76	Intermediate Similarity	NPC473780
0.76	Intermediate Similarity	NPC604521
0.7407	Intermediate Similarity	NPC485250
0.7407	Intermediate Similarity	NPC605396
0.7358	Intermediate Similarity	NPC25703
0.7347	Intermediate Similarity	NPC73310
0.7347	Intermediate Similarity	NPC473529
0.7347	Intermediate Similarity	NPC180363
0.7347	Intermediate Similarity	NPC94875
0.7347	Intermediate Similarity	NPC11332
0.7347	Intermediate Similarity	NPC145914
0.7347	Intermediate Similarity	NPC601174
0.7347	Intermediate Similarity	NPC601403
0.7347	Intermediate Similarity	NPC603568
0.7347	Intermediate Similarity	NPC604330
0.7347	Intermediate Similarity	NPC608300
0.7347	Intermediate Similarity	NPC611200
0.7347	Intermediate Similarity	NPC611571
0.7308	Intermediate Similarity	NPC81045
0.7308	Intermediate Similarity	NPC39754
0.7308	Intermediate Similarity	NPC171135
0.7308	Intermediate Similarity	NPC61257
0.7308	Intermediate Similarity	NPC320569
0.7308	Intermediate Similarity	NPC133730
0.7308	Intermediate Similarity	NPC191929
0.7308	Intermediate Similarity	NPC100454
0.7308	Intermediate Similarity	NPC242364
0.7308	Intermediate Similarity	NPC172821
0.7308	Intermediate Similarity	NPC156804
0.7308	Intermediate Similarity	NPC274446
0.7308	Intermediate Similarity	NPC485251
0.7308	Intermediate Similarity	NPC151403
0.7308	Intermediate Similarity	NPC261952
0.7308	Intermediate Similarity	NPC605171
0.717	Intermediate Similarity	NPC93794
0.717	Intermediate Similarity	NPC473504
0.717	Intermediate Similarity	NPC163093
0.717	Intermediate Similarity	NPC81778
0.717	Intermediate Similarity	NPC40066
0.717	Intermediate Similarity	NPC600524
0.717	Intermediate Similarity	NPC608355
0.7143	Intermediate Similarity	NPC473995
0.7018	Intermediate Similarity	NPC477014
0.7018	Intermediate Similarity	NPC477013
0.6949	Remote Similarity	NPC473905
0.6923	Remote Similarity	NPC329829
0.6923	Remote Similarity	NPC100921
0.6923	Remote Similarity	NPC477018
0.6909	Remote Similarity	NPC42598
0.6786	Remote Similarity	NPC329838
0.6786	Remote Similarity	NPC602738
0.678	Remote Similarity	NPC473520
0.661	Remote Similarity	NPC239517
0.6552	Remote Similarity	NPC169511
0.6552	Remote Similarity	NPC258068
0.6552	Remote Similarity	NPC287164
0.6552	Remote Similarity	NPC234077
0.6552	Remote Similarity	NPC476583
0.6545	Remote Similarity	NPC144415
0.6545	Remote Similarity	NPC607439
0.6545	Remote Similarity	NPC608157
0.6429	Remote Similarity	NPC241360
0.6429	Remote Similarity	NPC293136
0.6415	Remote Similarity	NPC606043
0.6316	Remote Similarity	NPC65930
0.6296	Remote Similarity	NPC107986
0.6296	Remote Similarity	NPC223871
0.6296	Remote Similarity	NPC231009
0.6296	Remote Similarity	NPC103284
0.6296	Remote Similarity	NPC110710
0.6296	Remote Similarity	NPC1083
0.6296	Remote Similarity	NPC82795
0.6296	Remote Similarity	NPC286338
0.6296	Remote Similarity	NPC603931
0.6296	Remote Similarity	NPC604237
0.623	Remote Similarity	NPC91067
0.6207	Remote Similarity	NPC309211
0.6207	Remote Similarity	NPC477010
0.6182	Remote Similarity	NPC488253
0.6182	Remote Similarity	NPC473669
0.6182	Remote Similarity	NPC488251
0.6129	Remote Similarity	NPC477015
0.6071	Remote Similarity	NPC232555
0.6071	Remote Similarity	NPC171174
0.6071	Remote Similarity	NPC114694
0.6071	Remote Similarity	NPC485248
0.6071	Remote Similarity	NPC142117
0.6071	Remote Similarity	NPC480249
0.6071	Remote Similarity	NPC485249
0.6071	Remote Similarity	NPC240695
0.6032	Remote Similarity	NPC473663
0.6032	Remote Similarity	NPC473723
0.6032	Remote Similarity	NPC475173
0.5968	Remote Similarity	NPC280612
0.5965	Remote Similarity	NPC488632
0.5965	Remote Similarity	NPC134865
0.5965	Remote Similarity	NPC103523
0.5965	Remote Similarity	NPC488627
0.5965	Remote Similarity	NPC488631
0.5965	Remote Similarity	NPC477011
0.5932	Remote Similarity	NPC329615
0.5882	Remote Similarity	NPC609415
0.5862	Remote Similarity	NPC280621
0.5862	Remote Similarity	NPC48338
0.5862	Remote Similarity	NPC488628
0.5846	Remote Similarity	NPC477017
0.5846	Remote Similarity	NPC477016
0.5789	Remote Similarity	NPC182383
0.5763	Remote Similarity	NPC178215
0.5763	Remote Similarity	NPC473687
0.5763	Remote Similarity	NPC204686
0.5763	Remote Similarity	NPC219498
0.5763	Remote Similarity	NPC308412
0.5763	Remote Similarity	NPC134885
0.5763	Remote Similarity	NPC488247
0.5763	Remote Similarity	NPC210218
0.5763	Remote Similarity	NPC488248
0.5667	Remote Similarity	NPC20621
0.5667	Remote Similarity	NPC318963
0.5667	Remote Similarity	NPC488250
0.5667	Remote Similarity	NPC605101
0.5645	Remote Similarity	NPC488623
0.5645	Remote Similarity	NPC488624
0.5645	Remote Similarity	NPC233551
0.5645	Remote Similarity	NPC40376
0.5645	Remote Similarity	NPC480082
0.5645	Remote Similarity	NPC21208
0.5645	Remote Similarity	NPC488629
0.5625	Remote Similarity	NPC253801
0.5574	Remote Similarity	NPC473478
0.5574	Remote Similarity	NPC69082
0.5574	Remote Similarity	NPC473651
0.5574	Remote Similarity	NPC488249
0.5574	Remote Similarity	NPC66346
0.5574	Remote Similarity	NPC477012
0.5484	Remote Similarity	NPC283085
0.5484	Remote Similarity	NPC130359
0.5484	Remote Similarity	NPC14901
0.5424	Remote Similarity	NPC47937
0.541	Remote Similarity	NPC134807
0.5397	Remote Similarity	NPC320458
0.5357	Remote Similarity	NPC112685
0.5333	Remote Similarity	NPC480079
0.5323	Remote Similarity	NPC20339
0.5283	Remote Similarity	NPC608138
0.5263	Remote Similarity	NPC480072
0.5238	Remote Similarity	NPC231096
0.5238	Remote Similarity	NPC475581
0.5238	Remote Similarity	NPC62118
0.5238	Remote Similarity	NPC132496
0.5238	Remote Similarity	NPC107717
0.5238	Remote Similarity	NPC488252
0.5231	Remote Similarity	NPC488630
0.5231	Remote Similarity	NPC488625
0.5231	Remote Similarity	NPC322529
0.5231	Remote Similarity	NPC488626
0.5079	Remote Similarity	NPC473707

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471567 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6692
0.1-0.2	2415
0.2-0.3	43
0.3-0.4	0
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data