NPASS Compound

Natural Product: NPC526804

Natural Product ID	NPC526804
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(1~{S},15~{R})-10,21,22,26-tetramethoxy-16,31-dimethyl-8,24-dioxa-16,31-diazaheptacyclo[23.6.2.1^{3,7}.1^{9,13}.1^{15,19}.0^{28,32}.0^{23,34}]hexatriaconta-3,5,7(36),9(35),10,12,19(34),20,22,25(33),26,28(32)-dodecaene
IUPAC Name	(1~{S},15~{R})-10,21,22,26-tetramethoxy-16,31-dimethyl-8,24-dioxa-16,31-diazaheptacyclo[23.6.2.1^{3,7}.1^{9,13}.1^{15,19}.0^{28,32}.0^{23,34}]hexatriaconta-3,5,7(36),9(35),10,12,19(34),20,22,25(33),26,28(32)-dodecaene
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 88 94 0 0 0 0 0 0 0 0999 V2000 3.0783 -5.9187 1.3136 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0902 -4.9088 0.3199 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8759 -4.2626 0.0230 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7115 -4.6028 0.6817 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4667 -3.9575 0.3745 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5342 -2.9518 -0.5965 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6317 -2.6320 -1.2346 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8160 -3.2761 -0.9305 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0331 -2.9742 -1.5649 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9870 -2.2101 -0.8533 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5524 -1.0112 -0.3588 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4020 -0.2149 0.3412 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6981 -0.6405 0.5359 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1844 -1.8401 0.0564 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2734 -2.6067 -0.6464 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9014 1.0775 0.8893 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2391 1.8554 -0.2085 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8019 2.0803 -0.0573 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1897 3.1540 -0.7214 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1662 3.3019 -0.5685 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9497 2.4511 0.2010 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3278 2.6823 0.2964 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9684 3.7379 -0.3511 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3394 1.4042 0.8460 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0304 1.2425 0.7020 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1144 0.5540 1.6085 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4318 0.2595 1.3352 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4160 0.6003 2.2403 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1044 1.2444 3.4473 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0617 2.6527 3.5710 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7444 0.3205 1.9923 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6930 0.6863 2.9403 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0661 0.4745 2.8424 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1075 -0.3157 0.8109 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1447 -0.6587 -0.0939 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7986 -0.3643 0.1826 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8480 -0.8210 -0.8935 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8200 -2.3122 -0.9039 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4329 -0.2929 -2.1164 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.4763 -0.4805 -3.1828 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6473 -0.9662 -2.5058 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5388 -1.3045 -1.3434 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0278 4.0599 -1.5485 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3402 4.2073 -0.8600 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9959 3.0490 -0.4331 N 0 0 0 0 0 0 0 0 0 0 0 0 5.3668 2.8797 -0.7287 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3809 -6.7211 0.9852 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1014 -6.3114 1.4655 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7012 -5.5462 2.2803 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7600 -5.3887 1.4400 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3533 -4.2663 0.9245 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7103 -1.8720 -2.0016 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5357 -0.7043 -0.5390 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3416 0.0448 1.1095 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2001 -2.1616 0.2149 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5493 -3.5758 -1.0710 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2684 0.9032 1.7837 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7546 1.6930 1.2776 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3441 1.2525 -1.1704 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6405 4.1425 -1.0887 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0699 3.5491 -0.2737 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6983 3.8037 -1.4255 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7734 4.6730 0.1995 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4344 0.3969 1.2417 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1927 3.1215 3.1074 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9635 3.1409 3.1288 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0914 2.8924 4.6461 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4777 0.6548 1.8440 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5602 1.1849 3.5571 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3275 -0.5601 3.2011 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1717 -0.5309 0.6300 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8805 -0.3488 -0.7598 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2326 -2.7490 -1.8445 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5508 -2.6821 -0.1164 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2968 -1.5724 -3.2819 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9033 -0.1712 -4.1759 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5231 0.0154 -2.9673 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2159 -0.2373 -3.1454 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4469 -1.8264 -3.1734 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5934 -2.4056 -1.2608 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6088 -1.0006 -1.5622 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2163 3.5241 -2.5039 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5750 5.0425 -1.6942 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0172 4.7348 -1.5992 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2996 4.9379 -0.0044 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9351 3.0231 0.2366 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8013 3.6227 -1.4244 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6167 1.8264 -1.0393 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 12 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 22 23 1 0 21 24 2 0 24 25 1 0 24 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 1 0 28 31 1 0 31 32 1 0 32 33 1 0 31 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 1 0 37 39 1 0 39 40 1 0 39 41 1 0 41 42 1 0 19 43 1 0 43 44 1 0 44 45 1 0 45 46 1 0 8 3 1 0 15 10 2 0 45 17 1 0 38 6 1 0 25 18 2 0 36 27 1 0 42 35 1 0 1 47 1 0 1 48 1 0 1 49 1 0 4 50 1 0 5 51 1 0 7 52 1 0 11 53 1 0 13 54 1 0 14 55 1 0 15 56 1 0 16 57 1 0 16 58 1 0 17 59 1 6 20 60 1 0 23 61 1 0 23 62 1 0 23 63 1 0 25 64 1 0 30 65 1 0 30 66 1 0 30 67 1 0 33 68 1 0 33 69 1 0 33 70 1 0 34 71 1 0 37 72 1 1 38 73 1 0 38 74 1 0 40 75 1 0 40 76 1 0 40 77 1 0 41 78 1 0 41 79 1 0 42 80 1 0 42 81 1 0 43 82 1 0 43 83 1 0 44 84 1 0 44 85 1 0 46 86 1 0 46 87 1 0 46 88 1 0 M END

Standard InCHIKey	WTXHFWYAETTXNF-XZWHSSHBSA-N
Standard InCHI	InChI=1S/C38H42N2O6/c1-39-14-12-25-20-32(42-4)34-22-28(25)29(39)17-23-8-7-9-27(16-23)45-33-19-24(10-11-31(33)41-3)18-30-36-26(13-15-40(30)2)21-35(43-5)37(44-6)38(36)46-34/h7-11,16,19-22,29-30H,12-15,17-18H2,1-6H3/t29-,30+/m0/s1
SMILES	COC1=CC=C2C=C1OC1=CC(=CC=C1)C[C@H]1C3=C(C=C(OC)C(=C3)OC3=C(OC)C(OC)=CC4=C3[C@@H](C2)N(C)CC4)CCN1C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	622.3	Volume:	649.006 ? Van der Waals volume.
Dense:	0.959	LogP:	3.918 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.403 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.868 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	42.0
TPSA:	61.86 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	7.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.238	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.722	Fsp³:	0.368
MCE-18:	129.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.997	Fluc inhibitor:	0.108 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.561 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.852 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.305

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.579	MDCK Permeability:	-4.661
Pgp-inhibitor:	0.975	Pgp-substrate:	0.423
PAMPA:	0.002 ? 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%):	0.119	30% Bioavailability (F30%):	0.151
50% Bioavailability (F50%):	0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.979	MRP1:	0.976
Plasma Protein Binding (PPB):	74.76%	Volume Distribution (VD):	0.144
Fu:	24.615% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.988
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.99
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.179
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.044
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.095
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.004
HLM stability:	0.515 ? 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):

9.804

Half-life (T1/2):

2.101

ADMET: Toxicity

hERG Blockers:	0.781	hERG Blockers (10um):	0.807
Human Hepatotoxicity (H-HT):	0.593	Drug-induced Liver Injury (DILI):	0.011
AMES Toxicity:	0.641	Rat Oral Acute Toxicity:	0.415
Maximum Recommended Daily Dose:	0.909	Skin Sensitization:	0.79
Carcinogencity:	0.748	Eye Corrosion:	0.0
Eye Irritation:	0.018	Respiratory Toxicity:	0.444
Drug-induced Neurotoxicity:	0.865	Ototoxicity:	0.65
Hematotoxicity:	0.154	Drug-induced Nephrotoxicity:	0.212
Genotoxicity:	0.059	RPMI-8226 Immunitoxicity:	0.069
A549 Cytotoxicity:	0.08	Hek293 Cytotoxicity:	0.595
BCF:	2.196 ? 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:	4.468 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.071 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.355 ? 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
NPO21435	Thalictrum faberi	Species	Ranunculaceae	Eukaryota	Roots	n.a.	n.a.	PMID[19299148]
NPO17909	Berberis vulgaris	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30701972]
NPO31374	Stephania cepharantha	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32129063]
NPO17909	Berberis vulgaris	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38731544]
NPO21435	Thalictrum faberi	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7528786]
NPO62587	Triclisia gilletii (De Wild.) Staner	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO62010	Stephania dicentrinifera H.S.Lo & M.Yang	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO64266	Stephania elegans Hook.& Thoms.	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO62485	Berberis glauca	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO53348	Stephania hainanensis H.S.Lo & Y.	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5144	Berberis japonica	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31374	Stephania cepharantha	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30288	Thalictrum thunbergii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21451	Thalictrum simplex	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16640	Thalictrum petaloideum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15847	Thalictrum glandulosissimum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13637	Thalictrum foliolosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7780	Thalictrum foetidum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21435	Thalictrum faberi	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13297	Thalictrum atriplex	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO42109	Stephania cepharantha Hayata	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO62488	Cocculus laurifolius DC.	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25761	Thalictrum microgynum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO42131	Limaciopsis loangensis Engl.	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO47699	Pycnarrhena australiana Muell.	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO53791	Mahonia siamensis Takeda(stem bark)	Genus	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30280	Mahonia japonica	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1843	Laurelia sempervirens	Species	Atherospermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18832	Berberis thunbergii	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO55007	Berberis sibirica	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO47980	Berberis poirettii	Genus	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO42552	Berberis candidula	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO64288	Berberis aemulans	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO62841	Stephania erecta Craib.	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO46059	Tiliacora funifera Engl.ex Diels	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO46294	Berberis vulgaris ssp.australis	Genus	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO48753	Stephania dielsiana Y.C.Wu	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO47254	Stephania pierrei Diels	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO47461	Stephania delavayi Diels	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO48269	Cyclea barbata Miers	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO48971	Pycnarrhena manillensis Vidal	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17909	Berberis vulgaris	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO61196	Stephania pierii	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16041	Berberis brandisiana	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO58774	Sinomenium diversifolium Diels	Genus	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21822	Berberis crataegina	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30288	Thalictrum thunbergii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30280	Mahonia japonica	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO13637	Thalictrum foliolosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21451	Thalictrum simplex	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7780	Thalictrum foetidum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16640	Thalictrum petaloideum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO31374	Stephania cepharantha	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15847	Thalictrum glandulosissimum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13297	Thalictrum atriplex	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21435	Thalictrum faberi	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO17909	Berberis vulgaris	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO25761	Thalictrum microgynum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18832	Berberis thunbergii	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21435	Thalictrum faberi	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13637	Thalictrum foliolosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7780	Thalictrum foetidum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16640	Thalictrum petaloideum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5144	Berberis japonica	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21451	Thalictrum simplex	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15847	Thalictrum glandulosissimum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13297	Thalictrum atriplex	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17909	Berberis vulgaris	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25761	Thalictrum microgynum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18832	Berberis thunbergii	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO30288	Thalictrum thunbergii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO30280	Mahonia japonica	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO31374	Stephania cepharantha	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO17909	Berberis vulgaris	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18832	Berberis thunbergii	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO13637	Thalictrum foliolosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO5144	Berberis japonica	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17909	Berberis vulgaris	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7780	Thalictrum foetidum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25761	Thalictrum microgynum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18832	Berberis thunbergii	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13637	Thalictrum foliolosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1843	Laurelia sempervirens	Species	Atherospermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21822	Berberis crataegina	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21451	Thalictrum simplex	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16041	Berberis brandisiana	Species	Berberidaceae	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

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

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 NPC526804 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	33108
0.1-0.2	16033
0.2-0.3	471
0.3-0.4	116
0.4-0.5	34
0.5-0.6	43
0.6-0.7	30
0.7-0.8	2
0.8-0.85	1
0.85-0.9	6
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8636	High Similarity	NPC76682
0.8636	High Similarity	NPC10908
0.8636	High Similarity	NPC63646
0.8636	High Similarity	NPC317145
0.8636	High Similarity	NPC198498
0.8636	High Similarity	NPC115284
0.8235	Intermediate Similarity	NPC276890
0.7534	Intermediate Similarity	NPC73492
0.7534	Intermediate Similarity	NPC299990
0.7534	Intermediate Similarity	NPC480587
0.726	Intermediate Similarity	NPC12424
0.726	Intermediate Similarity	NPC129518
0.726	Intermediate Similarity	NPC251580
0.7162	Intermediate Similarity	NPC603853
0.7123	Intermediate Similarity	NPC227060
0.7013	Intermediate Similarity	NPC185639
0.7013	Intermediate Similarity	NPC251735
0.7013	Intermediate Similarity	NPC49075
0.7013	Intermediate Similarity	NPC599951
0.6883	Remote Similarity	NPC311973
0.6842	Remote Similarity	NPC290582
0.6842	Remote Similarity	NPC217748
0.6842	Remote Similarity	NPC182052
0.6842	Remote Similarity	NPC271013
0.6842	Remote Similarity	NPC42663
0.6842	Remote Similarity	NPC15414
0.6795	Remote Similarity	NPC116465
0.6795	Remote Similarity	NPC223690
0.6795	Remote Similarity	NPC9532
0.6765	Remote Similarity	NPC247639
0.6765	Remote Similarity	NPC25084
0.6753	Remote Similarity	NPC279228
0.6567	Remote Similarity	NPC317439
0.6543	Remote Similarity	NPC16357
0.6543	Remote Similarity	NPC302245
0.6463	Remote Similarity	NPC323537
0.6456	Remote Similarity	NPC239824
0.6386	Remote Similarity	NPC485712
0.6375	Remote Similarity	NPC254441
0.6341	Remote Similarity	NPC195538
0.6265	Remote Similarity	NPC475479
0.6235	Remote Similarity	NPC10871
0.619	Remote Similarity	NPC24260
0.6163	Remote Similarity	NPC480586
0.6163	Remote Similarity	NPC480590
0.6104	Remote Similarity	NPC41376
0.6098	Remote Similarity	NPC229373
0.6071	Remote Similarity	NPC243454
0.6026	Remote Similarity	NPC603603
0.5882	Remote Similarity	NPC212237
0.5833	Remote Similarity	NPC181796
0.5833	Remote Similarity	NPC290005
0.5833	Remote Similarity	NPC54654
0.5833	Remote Similarity	NPC7715
0.5833	Remote Similarity	NPC328155
0.5833	Remote Similarity	NPC222661
0.5833	Remote Similarity	NPC285931
0.5814	Remote Similarity	NPC611658
0.573	Remote Similarity	NPC206900
0.5714	Remote Similarity	NPC274716
0.5714	Remote Similarity	NPC167116
0.5714	Remote Similarity	NPC609821
0.5672	Remote Similarity	NPC213206
0.5672	Remote Similarity	NPC188163
0.5672	Remote Similarity	NPC328750
0.5556	Remote Similarity	NPC281581
0.5506	Remote Similarity	NPC239584
0.5495	Remote Similarity	NPC485711
0.5488	Remote Similarity	NPC480591
0.5476	Remote Similarity	NPC475393
0.5455	Remote Similarity	NPC275680
0.5455	Remote Similarity	NPC22115
0.5443	Remote Similarity	NPC256012
0.5443	Remote Similarity	NPC610965
0.5376	Remote Similarity	NPC41122
0.5376	Remote Similarity	NPC318805
0.5375	Remote Similarity	NPC480592
0.5341	Remote Similarity	NPC139783
0.5341	Remote Similarity	NPC65312
0.5341	Remote Similarity	NPC611798
0.5294	Remote Similarity	NPC286119
0.5294	Remote Similarity	NPC314682
0.5281	Remote Similarity	NPC249996
0.5213	Remote Similarity	NPC475597
0.519	Remote Similarity	NPC30779
0.5111	Remote Similarity	NPC8836
0.5063	Remote Similarity	NPC317272
0.5063	Remote Similarity	NPC268503
0.5054	Remote Similarity	NPC11296
0.5054	Remote Similarity	NPC254581
0.5054	Remote Similarity	NPC274661
0.5054	Remote Similarity	NPC82457

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC526804 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4662
0.1-0.2	4327
0.2-0.3	147
0.3-0.4	8
0.4-0.5	2
0.5-0.6	1
0.6-0.7	0
0.7-0.8	2
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8636	High Similarity	NPD8099	Discontinued
0.7887	Intermediate Similarity	NPD8156	Discontinued
0.7067	Intermediate Similarity	NPD8095	Phase 1
0.5672	Remote Similarity	NPD4664	Clinical (unspecified phase)

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